TLR9 gene expression in immune cells of patients with psoriasis

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Abstract

Background. Psoriasis (skin lesions and psoriatic arthritis – PA) is a chronic inflammatory autoimmune disease that can be triggered by excessive activation of endosomal toll-like receptors (TLRs), mainly TLR9. Elevated TLR9 levels are observed in both PA and psoriasis. Therefore, studying the expression pattern of the TLR9 gene may help select therapies for patients with PA and psoriasis.

Aim. To study the expression pattern of the TLR9 gene in blood mononuclear cells of PA and psoriasis patients without joint involvement for possible use in the transition to targeted therapy.

Materials and methods. Mononuclear cells were isolated from the peripheral blood of 31 patients with psoriasis vulgaris without joint involvement, 45 patients with PA, and 20 healthy volunteers. TLR9 gene expression was analyzed by real-time polymerase chain reaction.

Results. A comparison of expression levels in PA patients and healthy volunteers showed that the expression level of TLR9 in PA patients was 591 times higher than that in healthy volunteers. The expression level of TLR9 in psoriasis patients without joint involvement was also significantly (423-fold) higher than that in healthy subjects.

Conclusion. TLR9 gene expression in mononuclear cells of psoriasis patients with severe skin lesions is similar to that in PA patients. High levels of TLR9 gene expression may be a marker of possible joint involvement in patients with psoriasis and indicate the need to reconsider the therapeutic approach to a particular patient.

About the authors

Svetlana N. Chebysheva

Sechenov First Moscow State Medical University (Sechenov University)

Author for correspondence.
Email: svetamma@gmail.com
ORCID iD: 0000-0001-5669-4214

Cand. Sci. (Med.)

Russian Federation, Moscow

Vladimir V. Sobolev

Center for Theoretical Problems of Physico-Chemical Pharmacology

Email: vlsobolew@gmail.com
ORCID iD: 0000-0003-4779-156X
SPIN-code: 3035-8570

Cand. Sci. (Biol.)

Russian Federation, Moscow

Elena V. Denisova

Center for Theoretical Problems of Physico-Chemical Pharmacology; Moscow Scientific and Practical Center of Dermatovenereology, and Cosmetology

Email: svetamma@gmail.com
ORCID iD: 0000-0002-4887-284X

Cand. Sci. (Med.)

Russian Federation, Moscow; Moscow

Anna G. Soboleva

Center for Theoretical Problems of Physico-Chemical Pharmacology; Avtsyn Research Institute of Human Morphology

Email: annasobo@mail.ru
ORCID iD: 0000-0002-9158-1933

Cand. Sci. (Biol.)

Russian Federation, Moscow; Moscow

Natalia A. Geppe

Sechenov First Moscow State Medical University (Sechenov University)

Email: geppe@mail.ru
ORCID iD: 0000-0003-0547-3686

D. Sci. (Med.), Prof.

Russian Federation, Moscow

Irina M. Korsunskaya

Center for Theoretical Problems of Physico-Chemical Pharmacology; Moscow Scientific and Practical Center of Dermatovenereology, and Cosmetology

Email: marykor@bk.ru
ORCID iD: 0000-0002-6583-0318

D. Sci. (Med.), Prof.

Russian Federation, Moscow; Moscow

References

  1. Mease PJ, Armstrong AW. Managing Patients with Psoriatic Disease: The Diagnosis and Pharmacologic Treatment of Psoriatic Arthritis in Patients with Psoriasis. Drugs. 2014;74(4):423-41. doi: 10.1007/s40265-014-0191-y
  2. Iwasaki A, Medzhitov R. Toll-like receptor control of the adaptive immune responses. Nat Immunol. 2004;5(10):987-95. doi: 10.1038/ni1112
  3. Rahmani F, Rezaei N. Therapeutic targeting of Toll-like receptors: a review of Toll-like receptors and their signaling pathways in psoriasis. Expert Rev Clin Immunol. 2016;12(12):1289-98. doi: 10.1080/1744666X.2016.1204232
  4. Nesterova AP, Yuryev A, Klimov EA, et al. Disease pathways: an atlas of human disease signaling pathways. Amsterdam (The Netherlands) and New York: Elsevier, 2019.
  5. Nesterova AP, Klimov EA, Zharkova M, et al. Diseases of the skin and subcutaneous tissue. Amsterdam (The Netherlands) and New York: Elsevier, 2019.
  6. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT Method. Methods. 2001;25(4):402-8. doi: 10.1006/meth.2001.1262
  7. Morizane S, Yamasaki K, Mühleisen B, et al. Cathelicidin antimicrobial peptide LL-37 in psoriasis enables keratinocyte reactivity against TLR9 ligands. J Invest Dermatol. 2012;132(1):135-43. doi: 10.1038/jid.2011.259
  8. Brencicova E, Diebold SS. Nucleic acids and endosomal pattern recognition: how to tell friend from foe? Front Cell Infect Microbiol. 2013;3(1):135-43. doi: 10.3389/fcimb.2013.00037
  9. Gilliet M, Lande R. Antimicrobial peptides and self-DNA in autoimmune skin inflammation. Curr Opin Immunol. 2008;20(4):401-7. doi: 10.1016/j.coi.2008.06.008
  10. Соболев В.В., Чебышева С.Н., Геппе Н.А., и др. Экспрессия гена TNF-α в иммунных клетках больных псориазом и псориатическим артритом. Медицинский совет. 2022;13:6-10 [Sobolev VV, Chebysheva SN, Geppe NA, et al. TNF-α gene expression in immune cells of patients with psoriasis and psoriatic arthritis. Meditsinskiy sovet = Medical Council. 2022;13:6-10 (in Russian)]. doi: 10.21518/2079-701X-2022-16-13-6-10
  11. Yamamoto T. Angiogenic and Inflammatory Properties of Psoriatic Arthritis. ISRN Dermatol. 2013;2013(1):1-7. doi: 10.1155/2013/630620
  12. Marinoni B, Ceribelli A, Massarotti MS, Selmi C. The Th17 axis in psoriatic disease: pathogenetic and therapeutic implications. Autoimmun Highlights. 2014;5(1):9-19. doi: 10.1007/s13317-013-0057-4
  13. Sobolev VV, Denisova EV, Chebysheva SN, et al. IL-6 Gene Expression as a Marker of Pathological State in Psoriasis and Psoriatic Arthritis. Bull Exp Biol Med. 2022;173(1):77-80. doi: 10.1007/s10517-022-05497-0
  14. Sobolev VV, Soboleva AG, Denisova EV, et al. Proteomic Studies of Psoriasis. Biomedicines. 2022;10(3):619. doi: 10.3390/biomedicines10030619
  15. Sobolev VV, Sautin ME, Piruzian ES, et al. IL-17 gene expression levels in atherosclerosis and psoriasis. Prime. 2015;5:34-8. Available at: https://www.prime-journal.com/il-17-gene-expressionlevels-in-atherosclerosis-and-psoriasis. Accessed: 13.08.2021.
  16. Стародубцева Н.Л., Миннибаев М.Т., Соболева А.Г., и др. Экспрессия интерлейкина-17 в коже больных псориазом. Современные проблемы дерматовенерологии, иммунологии и врачебной косметологии. 2011;2:38-41 [Starodubtseva NL, Minnibaev MT, Soboleva AG, et al. Ekspressiia interleikina-17 v kozhe bol'nykh psoriazom. Sovremennye problemy dermatovenerologii, immunologii i vrachebnoi kosmetologii. 2011;2:38-41 (in Russian)].
  17. Соболев В.В., Денисова Е.В., Корсунская И.М. Изменение экспрессии гена S100А8 под воздействием лазерного излучения низкой интенсивности у больных псориазом. Эффективная фармакотерапия. 2021;17:14-6 [Sobolev VV, Denisova EV, Korsunskaia IM. Izmenenie ekspressii gena S100A8 pod vozdeistviem lazernogo izlucheniia nizkoi intensivnosti u bol'nykh psoriazom. Effektivnaia farmakoterapiia. 2021;17:14-6 (in Russian)]. doi: 10.33978/2307-3586-2021-17-1-14-16
  18. Ильина С.А., Золотаренко А.Д., Пирузян А.Л., и др. Экспрессия генов S100A8 и S100A9 в пораженной псориатическим процессом коже. Технологии живых систем. 2010;7:45-51 [Il'ina SA, Zolotarenko AD, Piruzian AL, et al. Ekspressiia genov S100A8 i S100A9 v porazhennoi psoriaticheskim protsessom kozhe. Tekhnologii zhivykh sistem. 2010;7:45-51 (in Russian)].
  19. Соболев В.В., Денисова Е.В., Корсунская И.М. Изменение экспрессии гена STAT3 при лечении псориаза. Медицинский совет. 2020;12:71-4 [Sobolev VV, Denisova EV, Korsunskaya IM. Alteration of STAT3 gene expression in psoriasis treatment. Meditsinskiy sovet = Medical Council. 2020;12:71-4 (in Russian)]. doi: 10.21518/2079-701X-2020-12-71-74
  20. Sobolev V, Nesterova A, Soboleva A, et al. Analysis of PPARγ Signaling Activity in Psoriasis. Int J Mol Sci. 2021;22(16):8603. doi: 10.3390/ijms22168603
  21. Sobolev V, Nesterova A, Soboleva A, et al. The Model of PPARγ – Downregulated Signaling in Psoriasis. PPAR Res. 2020;2020(16):1-11. doi: 10.1155/2020/6529057
  22. Соболев В.В., Соболева А.Г., Потекаев Н.Н., и др. Анализ экспрессии гена PPARγ при лечении псориаза. Медицинский совет. 2021;8:82-7 [Sobolev VV, Soboleva AG, Potekaev NN, et al. PPARγ gene expression analysis in psoriasis treatment. Meditsinskiy sovet = Medical Council. 2021;8:82-7 (in Russian)]. doi: 10.21518/2079-701X-2021-8-82-87
  23. Sobolev V, Sakaniya L, Tretiakov A, et al. Association of GA genotype of SNP rs4680 in COMT gene with psoriasis. Arch Dermatol Res. 2019;311(4):309-15. doi: 10.1007/s00403-019-01904-1
  24. Mahil SK, Capon F, Barker JN. Update on psoriasis immunopathogenesis and targeted immunotherapy. Semin Immunopathol. 2016;38(1):11-27. doi: 10.1007/s00281-015-0539-8

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