Роль метаболитов триптофанового обмена и короткоцепочечных жирных кислот в патогенезе аутоиммунных заболеваний

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Аннотация

С каждым годом распространенность аутоиммунных заболеваний в мире неуклонно растет. Этиология и патогенез аутоиммунных заболеваний крайне сложные и во многом остаются неясными. Тем не менее, все больше данных исследований последних лет указывает на критическую роль микроорганизмов в формировании нормального иммунного ответа и аутоиммунных реакций в организме хозяина. При этом одна из ведущих ролей отводится кишечной микробиоте, представленной триллионами микробов, образующих широкий спектр сигнальных и иммуннорегуляторных метаболитов. Формируя сложную взаимозависимую систему “хозяин–микробиота”, симбиотические бактерии во многом определяют развитие и функционирование иммунных клеток человека. В настоящем обзоре мы рассматриваем роль кишечной микробиоты и ее ключевых метаболитов (а именно короткоцепочечных жирных кислот и метаболитов триптофана) в патогенезе аутоиммунных заболеваний и обсуждаем возможные механизмы влияния обозначенных сигнальных молекул на иммунные клетки хозяина.

Об авторах

О. П. Шатова

Российский национальный исследовательский медицинский университет им. Н.И. Пирогова; Российский университет дружбы народов им. Патриса Лумумбы; Национальный медицинский исследовательский центр эндокринологии

Email: shatova.op@gmail.com
Россия, Москва; Россия, Москва; Россия, Москва

Е. М. Ягодкина

Российский национальный исследовательский медицинский университет им. Н.И. Пирогова

Email: shatova.op@gmail.com
Россия, Москва

С. С. Кайдошко

Российский национальный исследовательский медицинский университет им. Н.И. Пирогова

Email: shatova.op@gmail.com
Россия, Москва

А. А. Заболотнева

Российский национальный исследовательский медицинский университет им. Н.И. Пирогова; Национальный медицинский исследовательский центр эндокринологии

Email: shatova.op@gmail.com
Россия, Москва; Россия, Москва

А. В. Шестопалов

Российский национальный исследовательский медицинский университет им. Н.И. Пирогова; Национальный медицинский исследовательский центр детской гематологии,
онкологии и иммунологии им. Дмитрия Рогачева; Национальный медицинский исследовательский центр эндокринологии

Email: shatova.op@gmail.com
Россия, Москва; Россия, Москва; Россия, Москва

Список литературы

  1. Nasonov EL, Aleksandrova EN, Novikov AA (2015) Autoimmune Rheumatic Diseases – Problems of Immunopathology and Personalized Treatment. Proceed Vestn Ross Akad Medi Nauk 70: 169–182. https://doi.org/10.15690/vramn.v70i2.1310
  2. Wang L, Wang FS, Gershwin ME (2015) Human autoimmune diseases: a comprehensive update. J Intern Med. 278: 369–395. https://doi.org/10.1111/joim.12395
  3. Bach JF (2018) The hygiene hypothesis in autoimmunity: the role of pathogens and commensals. Nat Rev Immunol 18: 105–120. https://doi.org/10.1038/nri.2017.111
  4. Schroeder BO, Bäckhed F (2016) Signals from the gut microbiota to distant organs in physiology and disease. Nat Med 10: 1079–1089. https://doi.org/10.1038/nm.4185
  5. Sharon G, Sampson TR, Geschwind DH, Mazmanian SK (2016) The Central Nervous System and the Gut Microbiome. Cell 167(4): 915–932. https://doi.org/10.1016/j.cell.2016.10.027
  6. Levy M, Kolodziejczyk AA, Thaiss CA, Elinav E (2017) Dysbiosis and the immune system. Nat Rev Immunol 17(4): 219–232. https://doi.org/10.1038/nri.2017.7
  7. Wang H, Wang G, Banerjee N, Liang Y, Du X, Boor PJ, Hoffman KL., Khan MF (2021) Aberrant Gut Microbiome Contributes to Intestinal Oxidative Stress, Barrier Dysfunction, Inflammation and Systemic Autoimmune Responses in MRL/Lpr Mice. Front Immunol 12: 651191. https://doi.org/10.3389/fimmu.2021
  8. Greiling TM, Dehner C, Chen X, Hughes K, Iñiguez AJ, Boccitto M, Ruiz DZ, Renfroe SC, Vieira SM, Ruff WE (2018) Commensal Orthologs of the Human Autoantigen Ro60 as Triggers of Autoimmunity in Lupus. Sci Transl Med 10: eaan2306. https://doi.org/10.1126/scitranslmed.aan2306
  9. Ruff WE, Dehner C, Kim WJ, Pagovich O, Aguiar CL, Yu AT, Roth AS, Vieira SM, Kriegel C, Adeniyi O (2019) Pathogenic Autoreactive T and B Cells Cross-React with Mimotopes Expressed by a Common Human Gut Commensal to Trigger Autoimmunity. Cell Host Microbe 26: 100–113.e8. https://doi.org/10.1016/j.chom.2019.05.003
  10. Horai R, Zárate-Bladés CR, Dillenburg-Pilla P, Chen J, Kielczewski JL, Silver PB, Jittayasothorn Y, Chan CC, Yamane H, Honda K (2015) Microbiota-Dependent Activation of an Autoreactive T Cell Receptor Provokes Autoimmunity in an Immunologically Privileged Site. Immunity 43: 343–353. https://doi.org/10.1016/j.immuni.2015.07.014
  11. Ruff WE, Kriegel MA (2015) Autoimmune Host-Microbiota Interactions at Barrier Sites and Beyond. Trends Mol Med 21: 233–244. https://doi.org/10.1016/j.molmed.2015.02.006
  12. Cayres LC, de Salis, Rodrigues GSP, Lengert A, Biondi APC, Sargentini LD, Brisotti JL, Gomes E, de Oliveira GL (2021) Detection of Alterations in the Gut Microbiota and Intestinal Permeability in Patients With Hashimoto Thyroiditis. Front Immunol 12: 579140. https://doi.org/10.3389/fimmu.2021.579140
  13. Yuan X, Wang R, Han B, Sun CJ, Chen R, Wei H, Chen L, Du H, Li G, Yang Y (2022) Functional and Metabolic Alterations of Gut Microbiota in Children with New-Onset Type 1 Diabetes. Nat Commun 13: 6356. https://doi.org/10.1038/s41467-022-33656-4
  14. Maffeis C, Martina A, Corradi M, Quarella S, Nori N, Torriani S, Plebani M, Contreas G, Felis GE (2016) Association between Intestinal Permeability and Faecal Microbiota Composition in Italian Children with Beta Cell Autoimmunity at Risk for Type 1 Diabetes. Diabetes Metab Res Rev 32: 700–709. https://doi.org/10.1002/dmrr.2790
  15. Siljander H, Honkanen J, Knip M (2019) Microbiome and Type 1 Diabetes. EBioMedicine 46: 512–521. https://doi.org/10.1016/j.ebiom.2019.06.031
  16. Walters WA, Xu Z, Knight R (2014) Meta-Analyses of Human Gut Microbes Associated with Obesity and IBD. FEBS Lett 588: 4223–4233. https://doi.org/10.1016/j.febslet.2014.09.039
  17. Viladomiu M, Kivolowitz C, Abdulhamid A, Dogan B, Victorio D, Castellanos JG, Woo V, Teng F, Tran NL, Sczesnak A (2017) IgA-Coated E. Coli Enriched in Crohn’s Disease Spondyloarthritis Promote TH17-Dependent Inflammation. Sci Transl Med 9: eaaf9655. https://doi.org/10.1126/scitranslmed.aaf9655
  18. Zhang X, Zhang D, Jia H, Feng Q, Wang D, Liang D, Wu X, Li J, Tang L, Li Y (2015) The Oral and Gut Microbiomes Are Perturbed in Rheumatoid Arthritis and Partly Normalized after Treatment. Nat Med 21: 895–905. https://doi.org/10.1038/nm.3914
  19. Taneja V (2014) Arthritis Susceptibility and the Gut Microbiome. FEBS Lett 588: 4244–4249. https://doi.org/10.1016/j.febslet.2014.05.034
  20. Gong B, Wang C, Meng F, Wang H, Song B, Yang Y, Shan Z (2021) Association Between Gut Microbiota and Autoimmune Thyroid Disease: A Systematic Review and Meta-Analysis. Front Endocrinol (Lausanne) 12: 774362. https://doi.org/10.3389/fendo.2021.774362
  21. Mu Q, Zhang H, Liao X, Lin K, Liu H, Edwards MR, Ahmed SA, Yuan R, Li L, Cecere TE (2017) Control of Lupus Nephritis by Changes of Gut Microbiota. Microbiome 5: 73. https://doi.org/10.1186/s40168-017-0300-8
  22. Dei-Cas I, Giliberto F, Luce L, Dopazo H, Penas-Steinhardt A (2020) Metagenomic Analysis of Gut Microbiota in Non-Treated Plaque Psoriasis Patients Stratified by Disease Severity: Development of a New Psoriasis-Microbiome Index. Sci Rep 10: 12754. https://doi.org/10.1038/s41598-020-69537-3
  23. Mondanelli G, Iacono A, Carvalho A, Orabona C, Volpi C, Pallotta MT, Matino D, Esposito S, Grohmann U (2019) Amino Acid Metabolism as Drug Target in Autoimmune Diseases. Autoimmun Rev 18: 334–348. https://doi.org/10.1016/j.autrev.2019.02.004
  24. Dadvar S, Ferreira DMS, Cervenka I, Ruas JL (2018) The Weight of Nutrients: Kynurenine Metabolites in Obesity and Exercise. J Int Med 284: 519–533. https://doi.org/10.1111/joim.12830
  25. Moffett JR, Arun P, Puthillathu N, Vengilote R, Ives JA, Badawy AAB, Namboodiri AM (2020) Quinolinate as a Marker for Kynurenine Metabolite Formation and the Unresolved Question of NAD+ Synthesis During Inflammation and Infection. Front Immunol 11: 31. https://doi.org/10.3389/fimmu.2020.00031
  26. Shestopalov AV, Shatova OP, Karbyshev MS, Gaponov AM, Moskaleva NE, Appolonova SA, Tutelyan AV, Makarov VV, Yudin SM, Roumiantsev SA (2021) “Kynurenine Switch” and Obesity. Bull Siber Med 20: 103–111. https://doi.org/10.20538/1682-0363-2021-4-103-111
  27. Hevia A, Milani C, López P, Cuervo A, Arboleya S, Duranti S, Turroni F, González S, Suárez A, Gueimonde M (2014) Intestinal Dysbiosis Associated with Systemic Lupus Erythematosus. mBio 5: e01548-14. https://doi.org/10.1128/mBio.01548-14
  28. Badawy AAB (2017) Kynurenine Pathway of Tryptophan Metabolism: Regulatory and Functional Aspects. Int J Tryptophan Res 10: 1178646917691938. https://doi.org/10.1177/1178646917691938
  29. Badawy AAB (2019) Tryptophan Metabolism: A Versatile Area Providing Multiple Targets for Pharmacological Intervention. Egypt J Basic Clin Pharmacol 9: https://doi.org/10.32527/2019/101415. 10.32527/2019/101415
  30. Yuasa HJ, Ball HJ (2015) Efficient Tryptophan-Catabolizing Activity Is Consistently Conserved through Evolution of TDO Enzymes, but Not IDO Enzymes. J Exp Zool B Mol Dev Evol 324: 128–140. https://doi.org/10.1002/jez.b.22608
  31. Alvarado DM, Chen B, Iticovici M, Thaker AI, Dai N, VanDussen KL, Shaikh N, Lim CK, Guillemin GJ, Tarr PI, Ciorba MA (2019) Epithelial Indoleamine 2,3-Dioxygenase 1 Modulates Aryl Hydrocarbon Receptor and Notch Signaling to Increase Differentiation of Secretory Cells and Alter Mucus-Associated Microbiota. Gastroenterology 157: 1093–1108.e11. https://doi.org/10.1053/j.gastro.2019.07.013
  32. Cecchi M, Paccosi S, Silvano A, Eid AH, Parenti A (2021) Dexamethasone Induces the Expression and Function of Tryptophan-2-3-Dioxygenase in SK-MEL-28 Melanoma Cells. Pharmaceuticals (Basel) 14: 211. https://doi.org/10.3390/ph14030211
  33. Savitz J (2020) The Kynurenine Pathway: A Finger in Every Pie. Mol Psychiatry 25: 131–147. https://doi.org/10.1038/s41380-019-0414-4
  34. Shatova OP, Shestopalov AV (2023) Tryptophan Metabolism: A New Look at the Role of Tryptophan Derivatives in the Human Body. Biol Bull Rev 13: 81–91. https://doi.org/10.1134/S2079086423020068
  35. Jamshed L, Debnath A, Jamshed S, Wish JV, Raine JC, Tomy GT, Thomas PJ, Holloway AC (2022) An Emerging Cross-Species Marker for Organismal Health: Tryptophan-Kynurenine Pathway. Int J Mol Sci 23: 6300. https://doi.org/10.3390/ijms23116300
  36. Chen Y, Guillemin GJ (2009) Kynurenine Pathway Metabolites in Humans: Disease and Healthy States. Int J Tryptophan Res 2: 1–19. https://doi.org/10.4137/ijtr.s2097
  37. Krupa A, Kowalska I (2021) The Kynurenine Pathwa – New Linkage between Innate and Adaptive Immunity in Autoimmune Endocrinopathies. Int J Mol Sci 22: 9879. https://doi.org/10.3390/ijms22189879
  38. Zádori D, Klivényi P, Szalárdy L, Fülöp F, Toldi J, Vécsei L (2012) Mitochondrial Disturbances, Excitotoxicity, Neuroinflammation and Kynurenines: Novel Therapeutic Strategies for Neurodegenerative Disorders. J Neurol Sci 322: 187–191. https://doi.org/10.1016/j.jns.2012.06.004
  39. Silva S, Shimizu JF, Oliveira DM, de Assis LR, de Bittar C, Mottin M, Sousa BK, de P Mesquita NC, Regasini LO, Rahal P (2019) A Diarylamine Derived from Anthranilic Acid Inhibits ZIKV Replication. Sci Rep 9: 17703. https://doi.org/10.1038/s41598-019-54169-z
  40. Marszalek-Grabska M, Walczak K, Gawel K, Wicha-Komsta K, Wnorowska S, Wnorowski A, Turski WA (2021) Kynurenine Emerges from the Shadows – Current Knowledge on Its Fate and Function. Pharmacol Ther 225: 107845. https://doi.org/10.1016/j.pharmthera.2021.107845
  41. Gao J, Xu K, Liu H, Liu G, Bai M, Peng C, Li T, Yin Y (2018) Impact of the Gut Microbiota on Intestinal Immunity Mediated by Tryptophan Metabolism. Front Cell Infect Microbiol 8: 13. https://doi.org/10.3389/fcimb.2018.00013
  42. Schiering C, Wincent E, Metidji A, Iseppon A, Li Y, Potocnik AJ, Omenetti S, Henderson CJ, Wolf CR, Nebert DW (2017) Feedback Control of AHR Signalling Regulates Intestinal Immunity. Nature 542: 242–245. https://doi.org/10.1038/nature21080
  43. Neavin DR, Liu D, Ray B, Weinshilboum RM (2018) The Role of the Aryl Hydrocarbon Receptor (AHR) in Immune and Inflammatory Diseases. Int J Mol Sci 19: 3851. https://doi.org/10.3390/ijms19123851
  44. Liu M, Nieuwdorp M, de Vos WM, Rampanelli E (2022) Microbial Tryptophan Metabolism Tunes Host Immunity, Metabolism, and Extraintestinal Disorders. Metabolites 12: 834. https://doi.org/10.3390/metabo12090834
  45. Horiuchi H, Kamikado K, Aoki R, Suganuma N, Nishijima T, Nakatani A, Kimura I (2020) Bifidobacterium Animalis Subsp. Lactis GCL2505 Modulates Host Energy Metabolism via the Short-Chain Fatty Acid Receptor GPR43. Sci Rep 10: 4158. https://doi.org/10.1038/s41598-020-60984-6
  46. Schilderink R, Verseijden C, Seppen J, Muncan V, van den Brink GR, Lambers TT, van Tol EA, de Jonge WJ (2016) The SCFA Butyrate Stimulates the Epithelial Production of Retinoic Acid via Inhibition of Epithelial HDAC. Am J Physiol Gastrointest Liver Physiol 310: 1138–1146. https://doi.org/10.1152/ajpgi.00411.2015
  47. Fattahi Y, Heidari HR, Khosroushahi AY (2020) Review of Short-Chain Fatty Acids Effects on the Immune System and Cancer. Food Biosci 38: 100793. https://doi.org/10.1016/j.fbio.2020.100793
  48. Parada Venegas D, De la Fuente MK, Landskron G, González MJ, Quera R, Dijkstra G, Harmsen HJM, Faber KN, Hermoso MA (2019) Corrigendum: Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases. Front Immunol 10: 1486. https://doi.org/10.3389/fimmu.2019.01486
  49. Singh N, Gurav A, Sivaprakasam S, Brady E, Padia R, Shi, Thangaraju M, Prasad PD, Manicassamy S, Munn DH (2014) Activation of Gpr109a, Receptor for Niacin and the Commensal Metabolite Butyrate, Suppresses Colonic Inflammation and Carcinogenesis. Immunity 40: 1486. https://doi.org/10.1016/j.immuni.2013.12.007
  50. Huang W, Man Y, Gao C, Zhou L, Gu J, Xu H, Wan Q, Long Y, Chai L, Xu Y (2020) Short-Chain Fatty Acids Ameliorate Diabetic Nephropathy via GPR43-Mediated Inhibition of Oxidative Stress and NF-κ B Signaling. Oxid Med Cell Longev 4074832. https://doi.org/10.1155/2020/4074832
  51. Kelly CJ, Zheng L, Campbell, EL, Saeedi B, Scholz CC, Bayless AJ, Wilson KE, Glover LE, Kominsky DJ, Magnuson A et al. (2015) Crosstalk between Microbiota-Derived Short-Chain Fatty Acids and Intestinal Epithelial HIF Augments Tissue Barrier Function. Cell Host Microbe 17(5): 662–671. https://doi.org/10.1016/j.chom.2015.03.005
  52. Li YJ, Chen X, Kwan TK, Loh YW, Singer J, Liu Y, Ma J, Tan J, Macia L, Mackay CR (2020) Dietary Fiber Protects against Diabetic Nephropathy through Short-Chain Fatty Acid-Mediated Activation of G Protein-Coupled Receptors GPR43 and GPR109A. J Am Soc Nephrol 31: 1267–1281. https://doi.org/10.1681/ASN.2019101029
  53. Williams SG, Wolin SL (2021) The Autoantigen Repertoire and the Microbial RNP World. Trends Mol Med 27: 422–435. https://doi.org/10.1016/j.molmed.2021.02.003
  54. Koga M, Gilbert M, Li Yuki N (2015) Complex of GM1-and GD1a-Likelipo-Oligosaccharide Mimics GM1b, Inducing Anti-GM1b Antibodies. PLoS One 10: e0124004. https://doi.org/10.1371/journal.pone.0124004
  55. Kiseleva EP, Mikhailopulo KI, Sviridov OV, Novik GI, Knirel YA, Dey ES (2011) The Role of Components of Bifidbacterium and Lactobacillus in Pathogenesis and Serologic Diagnosis of Autoimmune Thyroid Diseases. Benef Microbes 2: 139–154. https://doi.org/10.3920/BM2010.0011
  56. Elsayed NS, Aston P, Bayanagari VR, Shukla SK (2022) The Gut Microbiome Molecular Mimicry Piece in the Multiple Sclerosis Puzzle. Front Immunol 13: 972160. https://doi.org/10.3389/fimmu.2022.972160
  57. Kinashi Y, Hase K (2021) Partners in Leaky Gut Syndrome: Intestinal Dysbiosis and Autoimmunity. Front Immunol 12: 673708. https://doi.org/10.3389/fimmu.2021.673708
  58. Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA, Bohlooly YM, Glickman JN, Garrett WS (2013) The Microbial Metabolites, Short-Chain Fatty Acids, Regulate Colonic T Reg Cell Homeostasis. Science 341: 569–573. https://doi.org/10.1126/science.1241165
  59. Masetti G, Ludgate M. (2020) Microbiome and Graves’ Orbitopathy. Eur Thyroid J 9: 78–85. https://doi.org/10.1159/000512255
  60. Paray BA, Albeshr MF, Jan AT, Rather IA (2020) Leaky Gut and Autoimmunity: An Intricate Balance in Individuals Health and the Diseased State. Int J Mol Sci 21: 9770. https://doi.org/10.3390/ijms21249770
  61. Manfredo Vieira S, Hiltensperger M, Kumar V, Zegarra-Ruiz D, Dehner C, Khan N, Costa FRC, Tiniakou E, Greiling T, Ruff W (2018) Erratum: The Report “Translocation of a Gut Pathobiont Drives Autoimmunity in Mice and Humans”. Science 359(6380): 1156–1161. https://doi.org/10.1126/science.aar7201
  62. Kibbie JJ, Dillon SM, Thompson TA, Purba CM, McCarter MD, Wilson CC (2021) Butyrate Directly Decreases Human Gut Lamina Propria CD4 T Cell Function through Histone Deacetylase (HDAC) Inhibition and GPR43 Signaling. Immunobiology 226: 152126. https://doi.org/10.1016/j.imbio.2021.152126
  63. Kaisar MM, Pelgrom LR, van der Ham AJ, Yazdanbakhsh M, Everts B (2017) Butyrate Conditions Human Dendritic Cells to Prime Type 1 Regulatory T Cells via Both Histone Deacetylase Inhibition and G Protein-Coupled Receptor 109A Signaling. Front Immunol 8: 1429. https://doi.org/10.3389/fimmu.2017.01429
  64. Arpaia N, Campbell C, Fan X, Dikiy S, Van Der Veeken J, Deroos P, Liu H, Cross JR, Pfeffer K, Coffer PJ (2013) Metabolites Produced by Commensal Bacteria Promote Peripheral Regulatory T-Cell Generation. Nature 504: 451–455. https://doi.org/10.1038/nature12726
  65. Wu Y, Borde M, Heissmeyer V, Feuerer M, Lapan AD, Stroud JC, Bates DL, Guo L, Han A, Ziegler SF (2006) FOXP3 Controls Regulatory T Cell Function through Cooperation with NFAT. Cell 126: 375–387. https://doi.org/10.1016/j.cell.2006.05.042
  66. Raugh A, Allard D, Bettini M (2022) Nature vs. Nurture: FOXP3, Genetics, and Tissue Environment Shape Treg Function. Front Immunol 13: 911151. https://doi.org/10.3389/fimmu.2022.911151
  67. Fathi M, Vakili K, Yaghoobpoor S, Tavasol, Jazi K, Mohamadkhani A, Klegeris A, McElhinney A, Mafi Z, Hajiesmaeili M (2022) Dynamic Changes in Kynurenine Pathway Metabolites in Multiple Sclerosis: A Systematic Review. Front Immunol 13: 1013784. https://doi.org/10.3389/fimmu.2022.1013784
  68. Li H, Ning S, Ghandi M, Kryukov GV, Gopal S, Deik A, Souza A, Pierce K, Keskula P, Hernandez D (2019) The Landscape of Cancer Cell Line Metabolism. Nat Med 25: 850–860. https://doi.org/10.1038/s41591-019-0404-8
  69. Navarro MN, Gómez de las Heras MM, Mittelbrunn M. (2022) Nicotinamide Adenine Dinucleotide Metabolism in the Immune Response, Autoimmunity and Inflammageing. Br J Pharmacol 179: 1839–1856. https://doi.org/10.1111/bph.15477
  70. Grahnert A, Grahnert A, Klein C, Schilling E, Wehrhahn J, Hauschildt S (2011) NAD+: A Modulator of Immune Functions. Innate Immun 17: 212–233. https://doi.org/10.1177/1753425910361989
  71. Burns M, Ostendorf L, Biesen R, Grützkau A, Hiepe F, Mei HE, Alexander T (2021) Dysregulated Cd38 Expression on Peripheral Blood Immune Cell Subsets in Sle. Int J Mol Sci 22: 2424. https://doi.org/10.3390/ijms22052424
  72. Kar A, Mehrotra S, Chatterjee S (2020) CD38: T Cell Immuno-Metabolic Modulator. Cells 9: 1716. https://doi.org/10.3390/cells9071716
  73. Kwon HS, Lim HW, Wu J, Schnölzer M, Verdin E, Ott M (2012) Three Novel Acetylation Sites in the Foxp3 Transcription Factor Regulate the Suppressive Activity of Regulatory T Cells. J Immunol 188: 2712–2721. https://doi.org/10.4049/jimmunol.1100903
  74. Elkhal A, Biefer HRC, Heinbokel T, Uehara H, Quante M, Seyda M, Schuitenmaker JM, Krenzien F, Camacho V, De La Fuente MA (2016) NAD+ Regulates Treg Cell Fate and Promotes Allograft Survival via a Systemic IL-10 Production That Is CD4+ CD25+ Foxp3+ T Cells Independent. Sci Rep 6: 22325. https://doi.org/10.1038/srep22325
  75. Pallotta MT, Orabona C, Volpi C, Vacca C, Belladonna ML, Bianchi R, Servillo G, Brunacci C, Calvitti M, Bicciato S (2011) Indoleamine 2,3-Dioxygenase Is a Signaling Protein in Long-Term Tolerance by Dendritic Cells. Nat Immunol 12: 870–878. https://doi.org/10.1038/ni.2077
  76. Buonaguro L, Mayer-Mokler A, Flohr C, Reinhardt C, Singh-Jasuja H, Accolla R, Tosi G, Ma YT, Adams D, Valmori D (2017) Corrigendum to “New Vaccination Strategies in Liver Cancer”. Cytokine Growth Factor Rev 36: 125–129. https://doi.org/10.1016/j.Cytogfr.2017.06.010

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