Hormonal modulation of NK-cell plasticity during pregnancy

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The article presents a review of scientific studies on the effect of hormones produced by the placenta during physiological pregnancy on plasticity of NK cells, accompanied by a change in the phenotype and functional activity of the latter. Analysis of scientific studies has shown the primary role of estrogens, progesterone, human chorionic gonadotropin, leptin, ghrelin and kisspeptin in the induction of NK cell plasticity processes. Hormones are able to transform NK lymphocytes of peripheral blood into decidual (d)NK cells with reduced cytotoxicity, expression of inhibitory receptors and increased production of the fetoprotective cytokine TGF-b. At the same time, hormones reduce the production of such abortogenic cytokines as IL-17A and IFN-γ. The action of hormones is carried out in concentrations characteristic of pregnancy and is specific. In addition, hormones can recruit other cells of the placental microenvironment. In addition, hormones support the phenomenon of plasticity, exerting a similar effect on dNK cells, which apparently enhances the processes of immune tolerance towards the fetus and promotes its physiological development during pregnancy.

Sobre autores

S. Shirshev

Perm Federal Research Center of the Ural Branch of the Russian Academy of Sciences

Autor responsável pela correspondência
Email: Shirshev@iegm.ru

Institute of Ecology and Genetics of Microorganisms

Rússia, Perm

Bibliografia

  1. Blau HM, Pavlath GK, Hardeman EC, Chiu CP, Silberstein L, Webster SG, Miller SC, Webster C (1985) Plasticity of the differentiated state. Science 230: 758–766. https://doi.org/10.1126/science.2414846
  2. DuPage M, Bluestone JA (2016) Harnessing the plasticity of CD4+T cells to treat immune- mediated disease. Nat Rev Immunol 16: 149–163. https://doi.org/10.1038/nri.2015.18
  3. Sica A, Mantovani A (2012) Macrophage plasticity and polarization: in vivo veritas. J Clin Invest 122: 787–795. https://doi.org/10.1172/JCI59643
  4. Galli SJ, Borregaard N, Wynn TA (2011) Phenotypic and functional plasticity of cells of innate immunity: Macrophages, mast cells and neutrophils. Nat Immunol 12: 1035–1044. https://doi.org/10.1038/ni.2109
  5. Sharma S (2014) Natural killer cells and regulatory T cells in early pregnancy loss. Int J Dev Biol 58: 219–229. https://doi.org/10.1387/ijdb.140109ss
  6. Alijotas-Reig J, Llurba E, Gris JM (2014) Potentiating maternal immune tolerance in pregnancy: A new challenging role for regulatory T cells. Placenta 35: 241–248. https://doi.org/10.1016/j.placenta.2014.02.004
  7. Shirshev SV (2015) Molecular mechanisms of hormonal and hormonal-cytokine control of immune tolerance in pregnancy. Biochemistry (Moscow) Supp A: Membrane and Cell Biol 9: 21–39. https://doi.org/10.1134/S1990747814050079
  8. Gailly-Fabrea E, Kerlanb V, Christin-Maitrec S (2015) Hormones, grossesse et relation materno-foetale. Pregnancy-associated hormones and fetal-maternal relations. Ann Endocrinol 76: S39–S50. https://doi.org/10.1016/S0003-4266(16)30006-3
  9. Chantakru S, Wang W-C, van den Heuvel M, Bashar S, Simpson A, Chen Q, Croy BA, Evans SS (2003) Coordinate regulation of lymphocyte-endothelial interactions by pregnancy-associated hormones. J Immunol (Baltimore Md: 1950) 171: 4011–4019. https://doi.org/10.4049/jimmunol.171.8.4011
  10. Lee S, Kim J, Hur S, Kim C, Na B, Lee M, Gilman-Sachs A, Kwak-Kim J (2011) An imbalance in interleukin-17-producing T and Foxp3+ regulatory T cells in women with idiopathic recurrent pregnancy loss. Hum Reprod 26: 2964–2971. https://doi.org/10.1093/humrep/der301
  11. Santner-Nanan B, Straubinger K, Hsu P, Parnell G, Tang B, Xu B, Makris A, Hennessy A, Peek MJ, Busch DH, Prazeres da Costa C, Nanan R (2013) Fetal–maternal alignment of regulatory T cells correlates with IL-10 and Bcl-2 upregulation in pregnancy. J Immunol 191: 145–153. https://doi.org/10.4049/jimmunol 203165
  12. Tilburgs T, Scherjon SA, Claas FH (2010) Major histocompatibility complex (MHC)-mediated immune regulation of decidual leukocytes at the fetal–maternal interface. J Reprod Immunol 85: 58–62. https://doi.org/10.1016/j.jri.2010.01.005
  13. Girardi G, Yarilin D, Thurman JM, Holers VM, Salmon JE (2006) Complement activation induces dysregulation of angiogenic factors and causes fetal rejection and growth restriction. J Exp Med 203: 2165–2175. https://doi.org/10.1084/jem.20061022
  14. Zhou WH, Dong L, Du MR, Zhu XY, Li DJ (2008) Cyclosporin A improves murine pregnancy outcome in abortion-prone matings: Involvement of CD80/86 and CD28/CTLA-4. Reproduction 135: 385–395. https://doi.org/10.1530/REP-07-0063
  15. Ширшев СВ (2010) Механизмы иммунной толерантности при физиологически протекающей беременности. Успехи физиол наук 41: 75–93. [Shirshev SV (2010) Mechanisms of immune tolerance during physiologically normal pregnancy. Advanc Physiol Sci 41: 75–93. (In Russ)].
  16. Arck PC, Hecher K (2013) Fetomaternal immune cross-talk and its consequences for maternal and offspring's health. Nat Med 19: 548–556. https://doi.org/10.1038/nm.3160
  17. Vacca P, Chiossone L, Mingari MC, Moretta L (2019) Heterogeneity of NK cells and other innate lymphoid cells in human and murine decidua. Front Immunol 10: 170. https://doi.org/10.3389/fimmu.2019.00170
  18. Bald T, Pedde A-M, Corvino D, Böttcher JP (2020) The role of NK cell as central communicators in cancer immunity. Adv Immunol 147: 61–88. https://doi.org/10.1016/bs.ai.2020.06.002
  19. Dietl J, Hönig A, Kämmerer U, Rieger L (2006) Natural killer cells and dendritic cells at the human feto-maternal interface: An effective cooperation? Placenta 27: 341–347. https://doi.org/10.1016/j.placenta.2005.05.001
  20. Dogra P, Rancan C, Ma W, Toth M, Senda T, Carpenter DJ, Kubota M, Matsumoto R, Thapa P, Szabo PA, Li Poon MM, Li J, Arakawa-Hoyt J, Shen Y, Fong L, Lanier LL, Farber DL (2020) Tissue determinants of human NK cell development, function, and residence. Cell 180: 749–763.e13. https://doi.org/10.1016/j.cell.2020.01.022
  21. Meininger I, Carrasco A, Rao A, Soini T, Kokkinou E, Mjösberg J (2020) Tissue-specific features of innate lymphoid cells. Trends Immunol 41: 902–917. https://doi.org/10.1016/J.IT.2020.08.009
  22. Corvino D, Kumar A, Bald T (2022) Plasticity of NK cells in cancer. Front Immunol 13: 888313. https://doi.org/10.3389/fimmu.2022.888313
  23. Cooper MA, Fehniger TA, Caligiuri MA (2001) The biology of human natural killer cell subsets. Trends Immunol 22: 633–640. https://doi.org/10.1016/s1471-4906(01)02060-9
  24. Cooper MA, Fehniger TA, Turner SC, Chen KS, Ghaheri BA, Ghayur T, Carson WE, Caligiuri MA (2001) Human natural killer cells: A unique innate immunoregulatory role for the CD56(bright) subset. Blood 97: 3146–3151. https://doi.org/10.1182/blood.v97.10.3146
  25. Ochoa MC, Minute L, Rodriguez I, Garasa S, Perez-Ruiz E, Inogés S, Melero I, Berraondo P (2017) Antibody-dependent cell cytotoxicity: Immunotherapy strategies enhancing effector NK cells. Immunol Cell Biol 95: 347–355. https://doi.org/10.1038/icb.2017.6
  26. Romagnani C, Juelke K, Falco M, Morandi B, D’Agostino A, Costa R, Ratto G, Forte G, Carrega P, Lui G, Conte R, Strowig T, Moretta A, Münz C, Thiel A, Moretta L, Ferlazzo G (2007) CD56bright CD16- killer Ig-like receptor- NK cells display longer telomeres and acquire features of CD56dim NK cells upon activation. J Immunol (Baltimore Md: 1950) 178: 4947–4955. https://doi.org/10.4049/jimmunol.178.8.4947
  27. Freud AG, Mundy-Bosse BL, Yu J, Caligiuri MA (2017) The broad spectrum of human natural killer cell diversity. Immunity 47: 820–833. https://doi.org/10.1016/j.immuni.2017.10.008
  28. Hashemi E, Malarkannan S (2020) Tissue-resident NK cells: Development, maturation, and clinical relevance. Cancers (Basel) 12: 1553. https://doi.org/10.3390/cancers12061553
  29. Harmon C, Robinson MW, Fahey R, Whelan S, Houlihan DD, Geoghegan J, O'Farrelly C (2016) Tissue-resident Eomes(Hi) T-bet(lo) CD56(bright) NK cells with reduced proinflammatory potential are enriched in the adult human liver. Eur J Immunol 46: 2111–2120. https://doi.org/10.1002/eji.201646559
  30. Jabrane-Ferrat N (2019) Features of human decidual NK cells in healthy pregnancy and during viral infection. Front Immunol 10: 1397. https://doi.org/10.3389/fimmu.2019.01397
  31. Bal SM, Golebski K, Spits H (2020) Plasticity of innate lymphoid cell subsets. Nat Rev Immunol 20: 552–565. https://doi.org/10.1038/s41577-020-0282-9
  32. Cuff AO, Sillito F, Dertschnig S, Hall A, Luong TV, Chakraverty R, Male V (2019) The obese liver environment mediates conversion of NK cells to a less cytotoxic ILC1-like phenotype. Front Immunol 10: 2180. https://doi.org/10.3389/fimmu.2019.02180
  33. Cortez VS, Ulland TK, Cervantes-Barragan L, Bando JK, Robinette ML, Wang Q, White AJ, Gilfillan S, Cella M, Colonna M (2017) SMAD4 impedes the conversion of NK cells into ILC1-like cells by curtailing non-canonical TGF-b signaling. Nat Immunol 18: 995–1035. https://doi.org/10.1038/ni.3809
  34. Cerdeira AS, Rajakumar A, Royle CM, Lo A, Husain Z, Thadhani RI, Sukhatme VP, Karumanchi SA, Kopcow HD (2013) Conversion of peripheral blood NK cells to a decidual NK-like phenotype by a cocktail of defined factors. J Immunol 190: 3939–3948. https://doi.org/10.4049/jimmunol.1202582
  35. Golebski K, Ros XR, Nagasawa M, van Tol S, Heesters BA, Aglmous H, Kradolfer CMA, Shikhagaie MM, Seys S, Hellings PW, van Drunen CM, Fokkens WJ, Spits H, Bal SM (2019) IL-1b, IL-23, and TGF-b drive plasticity of human ILC2s towards IL-17- producing ILCs in nasal inflammation. Nat Commun 10: 2162. https://doi.org/10.1038/s41467-019-09883-7
  36. Parker ME, Barrera A, Wheaton JD, Zuberbuehler MK, Allan DSJ, Carlyle JR, Reddy TE, Ciofani M (2020) c-Maf regulates the plasticity of group 3 innate lymphoid cells by restraining the type 1 program. J Exp Med 217: e20191030. https://doi.org/10.1084/jem.20191030/132584
  37. Bal SM, Bernink JH, Nagasawa M, Groot J, Shikhagaie MM, Golebski K, van Drunen CM, Lutter R, Jonkers RE, Hombrink P, Bruchard M, Villaudy J, Munneke JM, Fokkens W, Erjefält JS, Spits H, Ros XR (2016) IL-1b, IL-4 and IL-12 control the fate of group 2 innate lymphoid cells in human airway inflammation in the lungs. Nat Immunol 17: 636–645. https://doi.org/10.1038/ni.3444
  38. Dogra P, Rancan C, Ma W, Toth M, Senda T, Carpenter DJ, Kubota M, Matsumoto R, Thapa P, Szabo PA, Li Poon MM, Li J, Arakawa-Hoyt J, Shen Y, Fong L, Lanier LL, Farber DL (2020) Tissue determinants of human NK cell development, function, and residence. Cell 180: 749–763.e13. http://doi.org/10.1016/j.cell.2020.01.022
  39. Pelletier A, Stockmann C (2022) The metabolic basis of ILC plasticity. Front Immunol 13: 858051. https://doi.org/10.3389/fimmu.2022.858051
  40. Vacca P, Mingari MC, Moretta L (2013) Natural killer cells in human pregnancy. J Reprod Immunol 97: 14–19. https://doi.org/10.1016/j.jri.2012.10.008
  41. Manaster I, Mandelboim O (2008) The unique properties of human NK cells in the uterine mucosa. Placenta 22 (Suppl A): S60–S66. https://doi.org/10.1016/j.placenta.2007.10.006
  42. Ordi J, Casals G, Ferrer B, Creus M, Guix C, Palacı´n A, Campo E, Balasch J (2006) Uterine (CD56+ ) natural killer cells recruitment: association with decidual reaction rather than embryo implantation. Am J Reprod Immunol 55: 369–377. https://doi.org/10.1111/j.1600-0897.2006.00377x
  43. Guo W, Li P, Zhao G, Fan H, Hu Y, Hou Y (2012) Glucocorticoid receptor mediates the effect of progesterone on uterine natural killer cells. Am J Reprod Immunol 67: 463–473. https://doi.org/10.1111/j.1600-0897.2012.01114.x
  44. Ozenci CC, Korgun ET, Demir R (2001) Immunohistochemical detection of CD45+, CD56+, and CD14+ cells in human decidua during early pregnancy. Early Pregnancy 5: 164–75.
  45. Le Bouteiller P, Siewiera J, Casart Y, Aguerre-Girr M, El Costa H, Berrebi A, Tabiasco J, Jabrane-Ferrat N (2011) The human decidual NK-cell response to virus infection: what can we learn from circulating NK lymphocytes? J Reprod Immunol 88: 170–175. https://doi.org/10.1016/j.jri.2010.12.005
  46. Vacca P, Pietra G, Falco M, Romeo E, Bottino C, Bellora F, Prefumo F, Fulcheri E, Venturini PL, Costa M, Moretta A, Moretta L, Mingari MC (2006) Analysis of natural killer cells isolated from human decidua: Evidence that 2B4 (CD244) functions as an inhibitory receptor and blocks NK-cell function. Blood 108: 4078–4085. https://doi.org/10.1182/blood-2006-04-017343
  47. Russell P, Anderson L, Lieberman D, Tremellen K, Yilmaz H, Cheerala B, Sacks G (2011) The distribution of immune cells and macrophages in the endometrium of women with recurrent reproductive failure I: Techniques. J Reprod Immunol 91: 90–102. https://doi.org/10.1016/j.jri.2011.03.013
  48. Keskin DB, Allan DS, Rybalov B, Andzelm MM, Stern JN, Kopcow HD, Koopman LA, Strominger JL (2007) TGFbeta promotes conversion of CD16+ peripheral blood NK cells into CD16- NK cells with similarities to decidual NK cells. Proc Natl Acad Sci U S A 104: 3378–3383. https://doi.org/10.1073/pnas.0611098104
  49. Acar N, Ustunel I, Demir R (2011) Uterine Natural killer (uNK)cells and their missions during pregnancy: A review. Acta Histochem 113: 82–91. https://doi.org/10.1016/j.acthis.2009.12.001
  50. Sentman CL, Meadows SK, Wira CR, Eriksson M (2004) Recruitment of uterine NK cells: induction of CXC chemokine ligands 10 and 11 in human endometrium by estradiol and progesterone. J Immunol 173: 6760–6766. https://doi.org/10.4049/jimmunol.173.11.6760
  51. Wang L, Li X, Zhao Y, Fang C, Lian Y, Gou W, Han T, Zhu X (2015) Insights into the mechanism of CXCL12-mediated signaling in trophoblast functions and placental angiogenesis. Acta Biochim Biophys Sin 47: 663–672. https://doi.org/10.1093/abbs/gmv064
  52. Berahovich RD, Zabel BA, Penfold MET, Lewen S, Wang Y, Miao Z, Gan L, Pereda J, Dias J, Slukvin II, McGrath KE, Jaen JC, Schall TJ (2010) CXCR7 Protein is not expressed on human or mouse leukocytes. J Immunol 185: 5130–5139. https://doi.org/10.4049/jimmunol.1001660
  53. Chantakru S, Kuziel WA, Maeda N, Croy BA (2001) A study on the density and distribution of uterine natural killer cells at mid pregnancy in mice genetically-ablated for CCR2, CCR 5 and the CCR5 receptor ligand, MIP-1 alpha. J Reprod Immunol 49: 33–47. https://doi.org/10.1016/s0165-0378(00)00076-0
  54. Trundley A, Moffett A (2004) Human uterine leukocytes and pregnancy. Tissue Antigens 63: 1–12. https://doi.org/10.1111/j.1399-0039.2004.00170.x
  55. Helige C, Ahammer H, Moser G, Hammer A, Dohr G, Huppertz B, Sedlmayr P (2014) Distribution of decidual natural killer cells and macrophages in the neighbourhood of the trophoblast invasion front: A quantitative evaluation. Hum Reprod 29: 8–17. https://doi.org/10.1093/humrep/det353
  56. Verma S, Hiby SE, Loke YW, King A (2000) Human decidual natural killer cells express the receptor for and respond to the cytokine interleukin 15. Biol Reprod 62: 959–968. https://doi.org/10.1095/biolreprod62.4.959
  57. Kitaya K, Nakayama T, Okubo T, Kuroboshi H, Fushiki S, Honjo H (2003) Expression of macrophage inflammatory protein-1beta in human endometrium: its role in endometrial recruitment of natural killer cells J Clin Endocrinol Metab 88: 1809–1814. https://doi.org/10.1210/jc.2002-020980
  58. Dietl J, Ruck P, Marzusch K, Horny HP, Kaiserling E, Handgretinger R (1992) Uterine granular lymphocytes are activated natural killer cells expressing VLA-1. Immunol Today 13: 236. https://doi.org/10.1016/0167-5699(92)90161-Y
  59. Hanna J, Goldman-Wohl D, Hamani Y, Avraham I, Greenfield C, Natanson-Yaron S, Prus D, Cohen-Daniel L, Arnon TI, Manaster I, Gazit R, Yutkin V, Benharroch D, Porgador A, Keshet E, Yagel S, Mandelboim O (2006) Decidual NK cells regulate key developmental processes at the human fetal-maternal interface. Nat Med 12: 1065–1074. https://doi.org/10.1038/nm1452
  60. Shemesh A, Tirosh D, Sheiner E, Tirosh NB, Brusilovsky M, Segev R, Rosental B, Porgador A (2015) First trimester pregnancy loss and the expression of alternatively spliced NKp30 Isoforms in maternal blood and placental tissue. Front Immunol 6: 189. https://doi.org/10.3389/fimmu.2015.00189
  61. Sun J, Yang M, Ban Y, Gao W, Song B, Wang Y, Zhang Y, Shao Q, Kong B, Qu X (2016) Tim-3 is upregulated in NK cells during early pregnancy and inhibits NK cytotoxicity toward trophoblast in galectin-9 dependent pathway. PloS One 11: e0147186. https://doi.org/10.1371/journal.pone.0147186
  62. Li YH, Zhou WH, Tao Y, Wang SC, Jiang YL, Zhang D, Piao HL, Fu Q, Li DJ, Du MR (2016) The Galectin-9/Tim-3 pathway is involved in the regulation of NK cell function at the maternal-fetal interface in early pregnancy. Cell Mol Immunol 13: 73–81. https://doi.org/10.1038/cmi.2014.12
  63. Anderson AC, Anderson DE, Bregoli L, Hastings WD, Kassam N, Lei C, Chandwaskar R, Karman J, Su EW, Hirashima M, Bruce JN, Kane LP, Kuchroo VK, Hafler DA (2007) Promotion of tissue inflammation by the immune receptor Tim-3 expressed on innate immune cells. Science 318: 1141–1143. https://doi.org/10.1126/science.1148536
  64. Hu XH, Tang MX, Mor G, Liao AH (2016) Tim-3: Expression on immune cells and roles at the maternal-fetal interface. J Reprod Immunol 118: 92–99. https://doi.org/10.1016/j.jri.2016.10.113
  65. Xu L, Huang Y, Tan L, Yu W, Chen D, Lu CC, He J, Wu G, Liu X, Zhang Y (2015) Increased Tim-3 Expression in peripheral NK cells predicts a poorer prognosis and Tim-3 blockade improves NK cell-mediated cytotoxicity in human lung adenocarcinoma. Int Immunopharmacol 29: 635–641. https://doi.org/10.1016/j.intimp.2015.09.017
  66. Xiong S, Sharkey AM, Kennedy PR, Gardner L, Farrell LE, Chazara O, Bauer J, Hiby SE, Colucci F, Moffett A (2013) Maternal uterine NK cell-activating receptor KIR2DS1 enhances placentation. J Clin Invest 123: 4264–4272. https://doi.org/10.1172/JCI68991
  67. Jabrane-Ferrat N, Siewiera J (2013) The up side of decidual natural killer cells: new developments in immunology of pregnancy. Immunology 141: 490–497. https://doi.org/10.1111/imm.12218
  68. Rajagopalan S, Bryceson YT, Kuppusamy SP, Geraghty DE, van der Meer A, Joosten I, Long EO (2006) Activation of NK cells by an endocytosed receptor for soluble HLA-G. PloS Biol 4: e9. https://doi.org/10.1371/journal.pbio.0040009
  69. Vacca P, Cantoni C, Prato C, Fulcheri E, Moretta A, Moretta L, Mingari MC (2008) Regulatory role of NKp44, NKp46, DNAM-1 and NKG2D receptors in the interaction between NK cells and trophoblast cells. Evidence for divergent functional profiles of decidual versus peripheral NK cells. Int Immunol 20: 1395–1405. https://doi.org/10.1093/intimm/dxn105
  70. Vacca P, Moretta L, Moretta A, Mingari MC (2011) Origin, phenotype and function of human natural killer cells in pregnancy. Trends Immunol 32: 517–523. https://doi.org/10.1016/j.it.2011.06.013
  71. Mincheva-Nilsson L (2021) Immunosuppressive protein signatures carried by syncytiotrophoblast-derived exosomes and their role in human pregnancy. Front Immunol 12: 717884. https://doi.org/10.3389/fimmu.2021.717884
  72. Mincheva-Nilsson L, Nagaeva O, Chen T, Stendahl U, Antsiferova J, Mogren I (2006) Placenta-derived soluble MHC class I chain-related molecules down-regulate NKG2D receptor on peripheral blood mononuclear cells during human pregnancy: A possible novel immune escape mechanism for fetal survival. J Immunol 176: 3585–3592. https://doi.org/10.4049/jimmunol.176.6.3585
  73. Hedlund M, Stenqvist A-C, Nagaeva O, Kjellberg L, Wulff M, Baranov V, Lucia Mincheva-Nilsson L (2009) Human placenta expresses and secretes NKG2D ligands via exosomes that down-modulate the cognate receptor expression: evidence for immunosuppressive function. J Immunol 183: 340–351. https://doi.org/10.4049/jimmunol.0803477
  74. Marlin R, Duriez M, Berkane N, de Truchis C, Madec Y, Reycuille M-A, Cummings J-S, Cannoul C, Quillay1 H, Sinoussi1 FOB, Nugeyre M-T, Menu1 E (2012) Dynamic shift from CD85j/ILT-2 to NKG2D NK receptor expression pattern on human decidual NK during the first trimester of pregnancy. PLoS One 7(1): e30017. https://doi.org/10.1371/journal.pone.0030017
  75. Koopman LA, Kopcow HD, Rybalov B, Boyson JE, Orange JS, Schatz F, Masch R, Lockwood CJ, Schachter AD, Park PJ, Strominger JL (2003) Human decidual natural killer cells are a unique NK subset with immunomodulatory potential. J Exp Med 198: 1201–1212. https://doi.org/10.1084/jem.20030305
  76. Lee C-L, Vijayan M, Wang X, Lam KKW, Koistinen H, Seppala M, Li RHW, Ng EHY, Yeung WSB, Chiu PCN (2019) Glycodelin-A stimulates the conversion of human peripheral blood CD16- CD56bright NK cell to a decidual NK cell-like phenotype. Hum Reprod (Oxford England) 34: 689–701. https://doi.org/10.1093/humrep/dey378
  77. Paust S, Gill HS, Wang BZ, Flynn MP, Moseman EA, Senman B, Szczepanik M, Telenti A, Askenase PW, Compans RW, von Andrian UH (2010) Critical role for the chemokine receptor CXCR6 in NK cell-mediated antigenspecific memory of haptens and viruses. Nat Immunol 11: 1127–1135. https://doi.org/10.1038/ni.1953
  78. Sun JC, Beilke JN, Lanier LL (2009) Adaptive immune features of natural killer cells. Nature 457: 557–561. https://doi.org/10.1038/nature07665
  79. Netea MG, Joosten LA, Latz E, Mills KH, Natoli G, Stunnenberg HG, O'Neill LAJ, Xavier RJ (2016) Trained immunity: A program of innate immune memory in health and disease. Science 352: aaf1098. https://doi.org/10.1126/science.aaf1098
  80. Gamliel M, Goldman-Wohl D, Isaacson B, Gur C, Stein N, Yamin R, Berger M, Grunewald M, Keshet E, Rais Y, Bornstein C, David E, Jelinski A, Eisenberg I, Greenfield C, Ben-David A, Imbar T, Gilad R, Haimov-Kochman R, Mankuta D, Elami-Suzin M, Amit I, Hanna JH, Yagel S, Mandelboim O (2018) Trained memory of human uterine NK cells enhances their function in subsequent pregnancies. Immunity 48: 951–962.e5. https://doi.org/10.1016/j.immuni.2018.03.030
  81. Wu M, Yin Y, Zhao M, Hu L, Chen Q (2013) The low expression of leukemia inhibitory factor in endometrium: possible relevant to unexplained infertility with multiple implantation failures. Cytokine 62: 334–349. https://doi.org/10.1016/j.cyto.2013.03.002
  82. Zhang X, Wei H (2021) Role of decidual natural killer cells in human pregnancy and related pregnancy complications. Front Immunol 12: 728291. https://doi.org/10.3389/fimmu.2021.728291
  83. Barry KC, Hsu J, Broz ML, Cueto FJ, Binnewies M, Combes AJ, Nelson AE, Loo K, Kumar R, Rosenblum MD, Alvarado MD, Wolf DM, Bogunovic D, Bhardwaj N, Daud AI, Ha PK, Ryan WR, Pollack JL, Samad B, Asthana S, Chan V, Krummel MF (2018) A Natural killer-dendritic cell axis defines checkpoint therapy-responsive tumor microenvironments. Nat Med 24: 1178–1191. https://doi.org/10.1038/s41591-018-0085-8
  84. Vacca P, Cantoni C, Vitale M, Prato C, Canegallo F, Fenoglio D, Ragni N, Moretta L, Mingari MC (2010) Crosstalk between decidual NK and CD14+ myelomonocytic cells results in induction of Tregs and immunosuppression. Proc Natl Acad Sci U S A 107: 11918–11923. https://doi.org/10.1073/pnas.1001749107
  85. Böttcher JP, Bonavita E, Chakravarty P, Blees H, Cabeza-Cabrerizo M, Sammicheli S, Rogers NC, Sahai E, Zelenay S, Reis e Sousa C (2018) NK Cells Stimulate Recruitment of cDC1 into the Tumor Microenvironment Promoting Cancer Immune Control. Cell 172: 1022–1037.e14. https://doi.org/10.1016/j.cell.2018.01.004
  86. Laskarin G, Redzovic A, Rubesa Z, Mantovani A, Allavena P, Haller H, Vlastelic I, Rukavina D (2008) Decidual natural killer cell tuning by autologous dendritic cells. Am J Reprod Immunol 59: 433–445. https://doi.org/10.1111/j.1600-0897.2008.00599.x
  87. Fuglsang J, Skjaerbaek C, Espelund U, Frystyk J, Fisker S, Flyvbjerg A, Ovesen P (2005) Ghrelin and its relationship to growth hormones during normal pregnancy. Clin Endocrinol (Oxf) 62: 554–559. https://doi.org/10.1111/j.1365-2265.2005.02257.x
  88. Littauer EQ, Skountzou I (2018) Hormonal regulation of physiology, innate immunity and antibody response to H1N1 influenza virus infection during pregnancy. Front Immunol 9: 2455. https://doi.org/10.3389/fimmu.2018.02455
  89. Pérez-Péreza A, Vilariño-Garcíaa T, Fernández-Riejosa P, Martín-Gonzálezb J, Segura-Egeab JJ, Sánchez-Margalet V (2017) Role of leptin as a link between metabolism and the immune system. Cytokine & Growth Factor Rev 35: 71–84. https://doi.org/10.1016/j.cytogfr.2017.03.001
  90. Stutte S, Ruf J, Kugler I, Ishikawa-Ankerhold H, Parzefall A, Marconi P, Maeda T, Kaisho T, Krug A, Popper B, Lauterbach H, Colonna M, von Andrian U, Brocker T (2021) Type I interferon mediated induction of somatostatin leads to suppression of ghrelin and appetite thereby promoting viral immunity in mice. Brain Behav Immun 95: 429–443. https://doi.org/10.1016/j.bbi.2021.04.018
  91. Uhlén M, Fagerberg L, Hallström BM, Lindskog C, Oksvold P, Mardinoglu A, Sivertsson A, Kampf C, Sjöstedt E, Asplund A, Olsson IM, Edlund K, Lundberg E, Navani S, Szigyarto CA-K, Odeberg J, Djureinovic D, Takanen JO, Hober S, Alm T, Edqvist P-H, Berling H, Tegel H, Mulder J, Rockberg J, Nilsson P, Schwenk JM, Hamsten M, von Feilitzen K, Forsberg M, Persson L, Johansson F, Zwahlen M, von Heijne G, Nielsen J, Pontén F (2015) Proteomics. Tissue-based map of the human proteome. Science 347: 1260419. https://doi.org/10.1126/science.1260419
  92. Wira CR, Rodriguez-Garcia M, Patel MV (2015) The role of sex hormones in immune protection of the female reproductive tract. Nat Rev Immunol 15: 217–230. https://doi.org/10.1038/nri3819
  93. Pérez-Pérez A, Toro A, Vilariño-García T, Maymó J, Guadix P, Dueñas JL, Fernández-Sánchez M, Varone C, Sánchez-Margalet V (2018) Leptin action in normal and pathological pregnancies. J Cell Mol Med 22: 716–727. https://doi.org/10.1111/jcmm.13369
  94. Oruç AS, Mert I, Akturk M, Aslan E, Polat B, Buyukkagnıcı U, Danışman N (2013) Ghrelin and motilin levels in hyperemesis gravidarum. Archiv Gynecol Obstet 287: 1087–1092. https://doi.org/10.1007/s00404-012-2705-8
  95. Myers MG, Jr (2004) Leptin receptor signaling and the regulation of mammalian physiology. Recent Prog Horm Res 59: 287–304. https://doi.org/10.1210/rp.59.1.287
  96. Trinh T, Broxmeyer HE (2021) Role for leptin and leptin receptors in stem cells during health and diseases. Stem Cell Rev Rep17: 511–522. https://doi.org/10.1007/s12015-021-10132-y
  97. Francisco V, Pino J, Campos-Cabaleiro V, Ruiz-Fernandez C, Mera A, Gonzalez-Gay MA, Gualillo O (2018) Obesity, fat mass and immune system: Role for leptin. Front Physiol 9: 640. https://doi.org/10.3389/fphys.2018.00640
  98. Naylor C, Petri WA, Jr (2016) Leptin regulation of immune responses. Trends Mol Med 22: 88–98. https://doi.org/10.1016/j.molmed.2015.12.001
  99. Tena-Sempere M (2013) Interaction between energy homeostasis and reproduction: Central effects of leptin and ghrelin on the reproductive axis. Horm Metab Res 45: 919–927. https://doi.org/10.1055/s-0033-1355399
  100. Gorbunova OL, Shirshev SV (2020) Role of kisspeptin in regulation of reproductive and immune reactions. Biochemistry (Mosc) 85: 839–853. https://doi.org/10.1134/S0006297920080015
  101. Horikoshi Y, Matsumoto H, Takatsu Y, Ohtaki T, Kitada C, Usuki S, Fujino M (2003) Dramatic elevation of plasma metastin concentrations in human pregnancy: metastin as a novel placenta-derived hormone in humans. J Clin Endocrinol Metab 2: 914–919. https://doi.org/10.1210/jc.2002-021235
  102. Arruvito L, Giulianelli S, Flores AC, Paladino N, Barboza M, Lanari C, Fainboim L (2008) NK cells expressing a progesterone receptor are susceptible to progesterone-induced apoptosis. J Immunol 180: 5746–5753. https://doi.org/10.4049/jimmunol.180.8.5746
  103. Ndiaye K, Poole DH, Walusimbi S, Cannon MJ, Toyokawa K, Maalouf SW, Dong J, Thomas P, Pate JL (2012) Progesterone effects on lymphocytes may be mediated by membrane progesterone receptors. J Reprod Immunol 95: 15–26. https://doi.org/10.1016/j.jri.2012.04.004
  104. Gong H, Chen Y, Xu J, Xie X, Yu D, Bei Yang B, Kuang H (2017) The regulation of ovary and conceptus on the uterine natural killer cells during early pregnancy. Reprod Biol Endocrinol 15: 73. https://doi.org/10.1186/s12958-017-0290-1
  105. Polese B, Gridelet V, Araklioti E, Martens H, Perrier d’Hauterive S, Geenen V (2014) The endocrine milieu and CD4 T-lymphocyte polarization during pregnancy. Front Endocrinol 5: 106. https://doi.org/10.3389/fendo.2014.00106
  106. Capellino S, Claus M, Watzl C (2020) Regulation of natural killer cell activity by glucocorticoids, serotonin, dopamine, and epinephrine. Cell Mol Immunol 17: 705–711. https://doi.org/10.1038/s41423-020-0477-9
  107. Mani S, Mermelstein P, Tetel M, Anesetti G (2012) Convergence of multiple mechanisms of steroid hormone action. Horm Metab Res 44: 569–576. https://doi.org/10.1055/s-0032-1306343
  108. Tan IJ, Peeva E, Zandman-Goddard G (2015) Hormonal modulation of the immune system – A spotlight on the role of progestogens. Autoimmun Rev 14: 536–542. https://doi.org/10.1016/j.autrev.2015.02.004
  109. Uchida H, Maruyama T, Nishikawa-Uchida S, Miyazaki K, Masuda H, Yoshimura Y (2013) Glycodelin in reproduction. Reprod Med Biol 12: 79–84. https://doi.org/10.1007/s12522-013-0144-2
  110. Hughes GC, Clark EA, Wong AH (2013) The intracellular progesterone receptor regulates CD4+ T cells and T cell-dependent antibody responses. J Leukoc Biol 93: 369–375. https://doi.org/10.1189/jlb.1012491
  111. Szekeres-Bartho J (2018) The role of progesterone in feto-maternal immunological cross talk. Med Princ Pract 27: 301–307. https://doi.org/10.1159/000491576
  112. Anderle C, Hammer A, Polgr B, Hartmann M, Wintersteiger R, Blaschitz A, Dohr G, Desoye G, Szekeres-Bartho J, Sedlmayr P (2008) Human trophoblast cells express the immunomodulator progesterone-induced blocking factor. J Reprod Immunol 79: 26–36. https://doi.org/10.1016/j.jri.2008.06.002
  113. Kozma N, Halasz M, Polgar B, Poehlmann TG, Markert UR, Palkovics T, Keszei M, Par G, Kiss K, Szeberenyi J, Grama L, Szekeres-Bartho J (2006) Progesterone-induced blocking factor activates STAT6 via binding to a novel IL-4 receptor. J Immunol 176: 819–826. https://doi.org/10.4049/jimmunol.176.2.819
  114. Sentman CL, Meadows SK, Wira CR, Eriksson M (2004) Recruitment of uterine NK cells: Induction of CXC chemokine ligands 10 and 11 in human endometrium by estradiol and progesterone. J Immunol (Baltimore, Md: 1950) 173: 6760–6766. https://doi.org/10.4049/jimmunol.173.11.6760
  115. Szekeres-Bartho J, Schindler AE (2019) Progestogens and immunology. Best Pract Res Clin Obstet Gynaecol 60: 17–23. https://doi.org/10.1016/j.bpobgyn.2019.07.001
  116. Wang F, Zhu H, Li B, Liu M, Liu D, Deng M, Wang Y, Xia X, Jiang Q, Chen D (2017) Effects of human chorionic gonadotropin, estradiol, and progesterone on interleukin-18 expression in human decidual tissues. Gynecol Endocrinol 33: 265–269. https://doi.org/10.1080/09513590.2016.1212829
  117. Yie SM, Xiao R, Librach CL (2006) Progesterone regulates HLA-G gene expression through a novel progesterone response element. Hum Reprod 21: 2538–2544. https://doi.org/10.1093/humrep/del126
  118. Favier B, Lemaoult J, Lesport E, Carosella ED (2010) ILT2/HLA-G interaction impairs NK-cell functions through the inhibition of the late but not the early events of the NK-cell activating synapse. FASEB J 24: 689–699. https://doi.org/10.1096/fj.09-135194
  119. Van der Meer A, Lukassen HGM, van Lierop MJC, Wijnands F, Mosselman S, Braat DDM, Joosten I (2004) Membrane-bound HLA-G activates proliferation and interferon-gamma production by uterine natural killer cells. Mol Hum Reprod 10: 189–195. https://doi.org/10.1093/molehr/gah032
  120. Cristiani CM, Palella E, Sottile R, Tallerico R, Garofalo C, Carbone E (2016) Human NK cell subsets in pregnancy and disease: toward a new biological complexity. Front Immunol 27: 656. https://doi.org/10.3389/fimmu.2016.00656
  121. Borzychowski AM, Chantakru S, Minhas K, Paffaro VA, Yamada AT, He H, Korach KS, Croy BA (2003) Functional analysis of murine uterine natural killer cells genetically devoid of oestrogen receptors. Placenta 24: 403–411. https://doi.org/10.1053/plac.2002.0924
  122. Wehner R, Dietze K, Bachmann M, Schmitz M (2011) The bidirectional crosstalk between human Dendritic cells and natural killer cells. J Innate Immunity 3: 258–263. https://doi.org/10.1159/000323923
  123. Pierdominici M, Maselli A, Colasanti T, Giammarioli AM, Delunardo F, Vacirca D, Sanchez M, Giovannetti A, Malorni W, Ortona E (2010) Estrogen receptor profiles in human peripheral blood lymphocytes. Immunol Lett 132: 79–85. https://doi.org/10.1016/j.imlet.2010.06.003
  124. Shirshev SV, Nekrasova IV, Zamorina SA, Gorbunova OL, Orlova EG, Maslennikova IL (2014) The role of pregnancy-associated hormones in regulation of expression of molecules responsible for NK cell functional activity. Dokl Biol Sci 457: 261–264. https://doi.org/10.1134/S0012496614040115
  125. Shirshev SV, Nekrasova IV, Gorbunova OL, Orlova EG (2016) The influence of chorionic gonadotropin and estriol on NK cell phenotype and functional activity. Human Physiol 42: 554–558. https://doi.org/10.1134/S0362119716050145
  126. Shirshev SV, Nekrasova IV, Gorbunova OL, Orlova EG (2017) Hormonal regulation of NK cell cytotoxic activity. Dokl Biol Sci 472: 28–30. https://doi.org/10.1134/S0012496617010021
  127. Shirshev SV, Nekrasova IV, Gorbunova OL, Orlova EG, Maslennikova IL (2017) MicroRNA in hormonal mechanisms of regulation of NK cell function. Dokl Biochem Biophys 474: 168–172. https://doi.org/10.1134/S160767291703005x
  128. Wang P, Gu Y, Zhang Q, Han Y, Hou J, Lin L, Wu C, Bao Y, Su X, Jiang M, Wang Q, Li N, Cao X (2012) Identification of resting and type I IFN-activated human NK cell miRNomes reveals microRNA-378 and microRNA-30e as negative regulators of NK cell cytotoxicity. J Immunol 189: 211–221. https://doi.org/10.4049/jimmunol.1200609
  129. Acevedo HF (2002) Human chorionic gonadotropin (hCG), the hormone of life and death: A review. J Exp Ther Oncol 2: 133–145. https://doi.org/10.1046/j.1359-4117.2002.01031.x
  130. Cole LA (2010) Biological functions of hCG and hCG-related molecules. Reprod Biol Endocrinol 8: 102. https://doi.org/10.1186/1477-7827-8-102
  131. Kane N, Kelly R, Saunders PTK, Critchley HOD (2009) Proliferation of uterine natural killer cells is induced by human chorionic gonadotropin and mediated via the mannose receptor. Endocrinology 150: 2882–2888. https://doi.org/10.1210/en.2008-1309
  132. Bansal AS, Bora SA, Saso S, Smith JR, Johnson MR, Thum M-Y (2012) Mechanism of human chorionic gonadotrophin mediated immunomodulation in pregnancy. Expert Rev Clin Immunol 8: 747–753. https://doi.org/10.1586/eci.12.77
  133. Ширшев СВ, Некрасова ИВ, Заморина СА, Горбунова ОЛ, Орлова ЕГ, Масленникова ИЛ (2014) Гормональный контроль экспрессии CCR7 и L-селектина на NK-клетках. Рос иммунол журн 8(17): 430–432. [Shirshev SV, Nekrasova IV, Zamorina SA, Gorbunova OL, Orlova EG, Maslennikova IL (2014) Hormonal control of CCR7 and L-selektin expression on NK cells. Russ J Immunol 8(17): 430–432. (In Russ)].
  134. Ewen CL, Kane KP, Bleackley RC (2012) A quarter century of granzymes. Cell Death Differ 19: 28–35. https://doi.org/10.1038/cdd.2011.153
  135. Gong J, Liu R, Zhuang R, Fang L, Xu Z, Jin L, Wang T, Song C, Yang K, Wei Y, Yang A, Jin B, Chen L (2012) miR-30c-1* promotes natural killer cell cytotoxicity against human hepatoma cells by targeting the transcription factor HMBOX1. Cancer Sci 103: 645–652. https://doi.org/10.1111/j.1349-7006.2012.02207.x
  136. Trotta R, Chen L, Ciarlariello D, Josyula S, Mao C, Costinean S, Yu L, Butchar JP, Tridandapani S, Croce CM, Caligiuri MA (2012) miR-155 regulates IFN-γ production in natural killer cells. Blood 119: 3478–3485. https://doi.org/10.1182/blood-2011-12-398099
  137. Elemam NM, Mekky RY, El-Ekiaby NM, El Sobky SA, El Din MAM, Esmat G, Abdelaziz AI (2015) Repressing PU.1 by miR-29a in NK cells of HCV patients, diminishes its cytolytic effect on HCV infected cell models. Hum Immunol 76: 687–694. https://doi.org/10.1016/j.humimm.2015.09.021
  138. De Knegt VE, Hedley PL, Kanters JK, Thagaard IN, Krebs L, Christiansen M, Lausten-Thomsen U (2021) The role of leptin in fetal growth during preeclampsia. Int J Mol Sci 22: 4569. https://doi.org/10.3390/ijms22094569
  139. Faggioni R, Fantuzzi G, Fuller J, Dinarello CA, Feingold KR, Grunfeld C (1998) IL-1 beta mediates leptin induction during inflammation. Am J Physiol 274: 204–208. https://doi.org/10.1152/ajpregu.1998.274.1.R204
  140. Sanchez-Margalet V, Martin-Romero C, Santos-Alvarez J, Goberna R, Najib S, Gonzalez-Yanes C (2003) Role of leptin as an immunomodulator of blood mononuclear cells: Mechanisms of action Clin Exp Immunol 133: 11–19. https://doi.org/10.1046/j.1365-2249.2003.02190.x
  141. Zhao Y, Sun R, You L, Gao C, Tian Z (2003) Expression of leptin receptors and response to leptin stimulation of human natural killer cell lines. Biochem Biophys Res Commun 300: 247–252. https://doi.org/10.1016/s0006-291x(02)02838-3
  142. La CA, Matarese G (2004) The weight of leptin in immunity. Nat Rev Immunol 4: 371–379. https://doi.org/10.1038/nri1350
  143. Lash GE, Robson SC, Bulmer JN (2010) Review: Functional role of uterine natural killer (uNK) cells in human early pregnancy decidua. Placenta 31 (Suppl): S87–S92. https://doi.org/10.1016/j.placenta.2009.12.022
  144. Wrann CD, Laue T, Hübner L, Kuhlmann S, Jacobs R, Goudeva L, Nave H (2012) Short-term and long-term leptin expo-sure differentially affect human natural killer cell immune functions. Am J Physiol Endocrinol Metab 302: E108–E116. https://doi.org/10.1152/ajpendo.00057.2011
  145. Lamas B, Goncalves-Mendes N, Nachat-Kappes R, Rossary A, Caldefie-Chezet F, Marie-Paule Vasson M-P, Farges M-C (2013) Leptin modulates dose-dependently the metabolic and cytolytic activities of NK-92 cells. J Cell Physiol 228: 1202–1209. https://doi.org/10.1002/jcp.24273
  146. Shirshev SV, Nekrasova IV, Orlova EG, Gorbunova OL (2017) Effects of Leptin and Ghrelin on the Expression of Membrane Molecules and Cytokine Production by NK Cells from the Peripheral Blood. Biochemistry (Moscow) Suppl Series A: Membrane and Cell Biol 11: 54–61. https://doi.org/10.1134/S199074781604019x
  147. Shirshev SV, Nekrasova IV, Orlova EG, Gorbunova OL (2016) Roles of leptin and ghrelin in the regulation of the phenotype and cytokine production by NK cells from peripheral blood. Dokl Biol Sci 470: 249–252. https://doi.org/10.1134/S0012496616050136
  148. Pereira S, Cline DL, Glavas MM, Covey SD, Kieffer TJ (2021) Tissue-specific effects of leptin on glucose and lipid metabolism. Endocr Rev 42: 1–28. https://doi.org/10.1210/endrev/bnaa027
  149. Schalla MA, Stengel A (2021) The role of the gastric hormones grelin and nesfatin-1 in reproduction. Int J Molec Sci 22: 11059. https://doi.org/10.3390/ijms22201.1059
  150. Dixit VD, Yang H, Cooper-Jenkins A, Giri BB, Patel K, Taub DD (2009) Reduction of T cell-derived ghrelin enhances proinflammatory cytokine expression: implications for age-associated increases in inflammation. Blood 113: 5202–5205. https://doi.org/10.1182/blood-2008-09-181255
  151. Leung PK, Chow KB, Lau P-N, Chu K-M, Chan C-B, Cheng CHK, Wise H (2007) The funcated ghrelin receptor polypeptide (GHS-R1b) acts as a dominant-negative mutant of the ghrelin receptor. Cell Signal 19: 1011–1022. https://doi.org/10.1016/j.cellsig.2006.11.011
  152. Colledge WH (2008) GPR54 and kisspeptins. Res Probl Cell Differ 46: 117–143. https://doi.org/10.1007/400-2007-050
  153. Dhillo WS, Murphy KG, Bloom SR (2007) The neuroendocrine physiology of kisspeptin in the human. Rev Endocrinol Metab Disord 8: 41–46. https://doi.org/10.1007/s11154-007-9029-1
  154. Sullivan-Pyke C, Haisenleder DJ, Senapati S, Nicolais O, Eisenberg E, Sammel MD, Barnhart KT (2018) Kisspeptin as a new serum biomarker to discriminate miscarriage from viable intrauterine pregnancy. Fertil Steril 109: 137–141. https://doi.org/10.1016/j.fertnstert.2017.09.029
  155. Kotani M, Detheux M, Vandenbogaerde A, Le Poul E, Brézillon S, Tyldesley R, Suarez-Huerta N, Vandeput F, Blanpain C, Schiffmann SN, Vassart G, Parmentier M (2001) The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J Biol Chem 276: 34631–34636. https://doi.org/10.1074/jbc.M104847200
  156. Park DW, Lee SK, Hong SR, Han AR, KwakKim J, Yang KM (2012) Expression of kisspeptin and its receptor GPR54 in the first trimester trophoblast of women with recurrent pregnancy loss. Am J Reprod Immun 67: 132–139. https://doi.org/10.1111/j.1600-0897.2011.01073.x
  157. Shirshev SV, Nekrasova IV, Gorbunova OL, Orlova EG, Maslennikova IL (2015) The effect of kisspeptin on the functional characteristics of isolated NK cells. Dokl Biol Sci 464: 267–269. https://doi.org/10.1134/S0012496615050129
  158. Mailliard RB, Alber SM, Shen H, Watkins SC, Kirkwood JM, Herberman RB, Kalinski P (2005) IL-18-induced CD83+CCR7+NK helper cells. J Exp Med 202: 941–953. https://doi.org/10.1084/jem.20050128
  159. Holtan SG, Creedon DJ, Haluska P, Markovic SN (2009) Cancer and pregnancy: Parallels in growth, invasion, and immune modulation and implications for cancer therapeutic agents. Mayo Clin Proc 84: 985–1000. https://doi.org/10.1016/S0025-6196(11)60669-1
  160. Nurzadeh M, Ghalandarpoor-Attar SM, Ghalandarpoor-Attar SN, Rabiei M (2023) The role of interferon (IFN)-gamma in extravillous trophoblast cell (EVT) invasion and preeclampsia progression. Reprod Sci 30: 1462–1469. https://doi.org/10.1007/s43032-022-01110-x
  161. Pelletier A, Stockmann C (2022) The Metabolic Basis of ILC Plasticity. Front Immunol 13: e858051. https://doi.org/10.3389/fimmu.2022.858051
  162. Larson C, Oronsky B, Carter CA, Oronsky A, Knox SJ, Sher D, Reid TR (2020) TGF-beta: A master immune regulator. Expert Opin Ther Targets 24: 427–438. https://doi.org/10.1080/14728222.2020.1744568

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