PHENOTYPIC AND FUNCTIONAL CHARACTERISTICS OF EARLY THYMIC EMIGRANTS IN PERIPHERAL BLOOD IN NORMAL CONDITIONS AND AUTOIMMUNE DISEASES



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Abstract

Abstract

Complex mechanisms of thymus functioning affect the structural matrix, contributing to the gradual accumulation of genetic mutations, changes in gene expression and premature immunosenescence. The study of early thymic migrants (RTE) is necessary to identify possible diagnostic biomarkers and potential checkpoints of autoimmune diseases. The object of the study were peripheral blood samples of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasis (PS) and healthy donors. The aim of the study was to assess the ratio of recently migrated cells from the thymus and naive T-regulatory cells in the periphery in health and autoimmune pathology. The relative number of recent thymic migrants CD4+CD45RA+CD31+ (RTE) and the number of Foxp3+ T-regulatory cells (Treg) among them were determined by flow cytofluorimetry. The number of proliferating cells was determined by the intracellular Ki-67 content. The analysis showed that the number of RTE was reduced in the group of patients with RA and patients with PsA relative to the donor group (17.3%, 18.6% vs. 23.6%) and did not change significantly in patients with psoriasis. There were no significant differences between donors and patients with AID in the number of proliferating RTE and Tregs. The level of proliferation of T-regulatory cells in patients with psoriatic pathology was comparable to donor values, and in RA there was a tendency to an increase. In patients with RA, the number of proliferating naive Foxp3+ Tregs was significantly higher than the number of proliferating RTE (15.8% vs 3.1%, p<0.05, respectively). A decrease in the relative number of RTE  in AID may be associated with the activation of T lymphocytes and an increase in the proportion of central memory T cells. The number of Tregs among RTE and the level of their proliferation in patients with psoriatic pathology, indicate the absence of disturbances in the generation of T-reg in the thymus. The ambiguous results obtained in patients with RA, require additional confirmation on a larger sample of patients.

About the authors

Tatiana Yakovlevna Abramova

Federal State Budgetary Scientific Institution «Research Institute of Fundamental and Clinical Immunology» (RIFCI)

Email: tatjana-abramova@mail.ru
ORCID iD: 0000-0002-6947-2212

M.D., PhD, D.Sc., leading researcher in the laboratory of clinical immunopathology

Russian Federation, 630099, Russia, Novosibirsk, Yadrintsevskaya street, 14

Olga Sergeevna Boeva

Federal State Budgetary Scientific Institution «Research Institute of Fundamental and Clinical Immunology» (RIFCI)

Email: starchenkova97@gmail.com
ORCID iD: 0000-0003-2720-0961

PhD-student, the laboratory of clinical immunopathology

Russian Federation, 630099, Russia, Novosibirsk, Yadrintsevskaya street, 14

Olga Aleksandrovna Angelskaya

State Budgetary Health Institution of the Novosibirsk Region "City Hospital No3"

Email: anolga@mail.ru
ORCID iD: 0009-0002-7624-2279

dermatovenerologist

Russian Federation, 630056 Russia, Novosibirsk, Mukhacheva str. 5/4

Vadim Igorevich Borisevich

Novosibirsk State Medical Universit

Email: borvad2001@mail.ru
ORCID iD: 0009-0001-2731-6887

student

Russian Federation, 630091 Russia, Novosibirsk, Krasny Prospect str. 52

Veronika Sergeevna Abbasova

Novosibirsk State Medical Universit

Email: abbasovaveronik@gmail.com
ORCID iD: 0009-0003-6038-4990

student

Russian Federation, 630091 Russia, Novosibirsk, Krasny Prospect str. 52

Maksim Alexandrovich Korolev

Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Science (RICEL - Branch of IC&G SB RAS)

Email: kormax@bk.ru
ORCID iD: 0000-0002-4890-0847

MD., PhD, D.Sc., Deputy Head, Rheumatologist, Head of the sci. collaborator lab. connective tissue pathology of RICEL - Branch of IC&G SB RAS, Chief Rheumatologist of the Ministry of Health of the Novosibirsk Region

Russian Federation, 630117 Russia, Novosibirsk, 6 Arbuzova str. 6

Vitaliy Olegovich Omelchenko

Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Science (RICEL - Branch of IC&G SB RAS)

Email: v.o.omelchenko@gmail.com
ORCID iD: 0000-0001-6606-7185

MD Ph.D, rheumatologist, department of rheumatology, sci. collaborator lab. connective tissue pathology of RICEL - Branch of IC&G SB RAS

Russian Federation, 630117 Russia, Novosibirsk, 6 Arbuzova str. 6

Yuliya Dmitrievna Kurochkina

Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Science (RICEL - Branch of IC&G SB RAS)

Email: juli_k@bk.ru
ORCID iD: 0000-0002-7080-777X

MD, Ph.D., rheumatologist, department of rheumatology, sci. collaborator lab. pathology of connective tissue of RICEL - Branch of IC&G SB RAS

Russian Federation, 630117 Russia, Novosibirsk, 6 Arbuzova str. 6

Anna Dmitrievna Rybakova

Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Science (RICEL - Branch of IC&G SB RAS)

Email: a.rybakova1@g.nsu.ru

junior researcher of the laboratory of pharmacological modeling and screening of bioactive molecules of  RICEL - Branch of IC&G SB RAS

Russian Federation, 630117 Russia, Novosibirsk, 6 Arbuzova str. 6

Elena Andreevna Blinova

Federal State Budgetary Scientific Institution «Research Institute of Fundamental and Clinical Immunology» (RIFCI)

Author for correspondence.
Email: blinovaelena-85@yandex.ru
ORCID iD: 0000-0003-3327-3630

PhD, senior researcher in the laboratory of clinical immunopathology

Russian Federation, 630099, Russia, Novosibirsk, Yadrintsevskaya street, 14

References

  1. 1. Ao YQ, Jiang JH, Gao J, Wang HK, Ding JY. Recent thymic emigrants as the bridge between thymoma and autoimmune diseases. Biochim Biophys Acta Rev Cancer. 2022 May;1877(3):188730. Epub 2022 Apr 22. Erratum in: Biochim Biophys Acta Rev Cancer. 2022 Sep;1877(5):188780. doi: 10.1016/j.bbcan.2022.188730.
  2. doi: 10.1016/j.bbcan.2022.188780. PMID: 35469968.
  3. Azevedo RI, Soares MV, Barata JT, Tendeiro R, Serra-Caetano A, Victorino RM, Sousa AE. IL-7 sustains CD31 expression in human naive CD4+ T cells and preferentially expands the CD31+ subset in a PI3K-dependent manner. Blood. 2009 Mar 26;113(13):2999-3007. Epub 2008 Nov 13. doi: 10.1182/blood-2008-07-166223.
  4. PMID: 19008454.
  5. 2. Houston EG Jr, Fink PJ. MHC drives TCR repertoire shaping, but not maturation, in recent thymic emigrants. J Immunol. 2009 Dec 1;183(11):7244-9. Epub 2009 Nov 13. doi: 10.4049/jimmunol.0902313. PMID: 19915060; PMCID: PMC2782759.
  6. 3. James KD, Cosway EJ, Lucas B, White AJ, Parnell SM, Carvalho-Gaspar M, Tumanov AV, Anderson G, Jenkinson WE. Endothelial cells act as gatekeepers for LTβR-dependent thymocyte emigration. J Exp Med. 2018 Dec 3;215(12):2984-2993. Epub 2018 Nov 13. doi: 10.1084/jem.20181345. PMID: 30425120; PMCID: PMC6279407.
  7. 4. James KD, Cosway EJ, Parnell SM, White AJ, Jenkinson WE, Anderson G. Assembling the thymus medulla: Development and function of epithelial cell heterogeneity. Bioessays. 2024 Mar;46(3):e2300165. Epub 2023 Dec 31. doi: 10.1002/bies.202300165. PMID: 38161233; PMCID: PMC11475500.
  8. Junge S, Kloeckener-Gruissem B, Zufferey R, Keisker A, Salgo B, Fauchere JC, Scherer F, Shalaby T, Grotzer M, Siler U, Seger R, Güngör T. Correlation between recent thymic emigrants and CD31+ (PECAM-1) CD4+ T cells in normal individuals during aging and in lymphopenic children. Eur J Immunol. 2007 Nov;37(11):3270-80. doi: 10.1002/eji.200636976. PMID: 17935071.
  9. 5. Kohler S, Thiel A. Life after the thymus: CD31+ and CD31- human naive CD4+ T-cell subsets. Blood. 2009 Jan 22;113(4):769-74. Epub 2008 Jun 26. doi: 10.1182/blood-2008-02-139154. PMID: 18583570.
  10. 6. Kolerova A.V., Mikailova D.A., Beimanova M.A., Blinova E.A. Сharacterization of central and effector cd4⁺ memory cells in psoriasis. Medical Immunology (Russia). 2021;23(4):969-974. https://doi.org/10.15789/1563-0625-COC-2288.
  11. Legoux FP, Lim JB, Cauley AW, Dikiy S, Ertelt J, Mariani TJ, Sparwasser T, Way SS, Moon JJ. CD4+ T Cell Tolerance to Tissue-Restricted Self Antigens Is Mediated by Antigen-Specific Regulatory T Cells Rather Than Deletion. Immunity. 2015 Nov 17;43(5):896-908. Epub 2015 Nov 10. doi: 10.1016/j.immuni.2015.10.011. PMID: 26572061; PMCID: PMC4654997.
  12. Paiva RS, Lino AC, Bergman ML, Caramalho I, Sousa AE, Zelenay S, Demengeot J. Recent thymic emigrants are the preferential precursors of regulatory T cells differentiated in the periphery. Proc Natl Acad Sci U S A. 2013 Apr 16;110(16):6494-9. Epub 2013 Apr 1. doi: 10.1073/pnas.1221955110. PMID: 23576744; PMCID: PMC3631617.
  13. Silva SL, Albuquerque AS, Matoso P, Charmeteau-de-Muylder B, Cheynier R, Ligeiro D, Abecasis M, Anjos R, Barata JT, Victorino RM, Sousa AE. IL-7-Induced Proliferation of Human Naive CD4 T-Cells Relies on Continued Thymic Activity. Front Immunol. 2017 Jan 19;8:20. doi: 10.3389/fimmu.2017.00020. PMID: 28154568; PMCID: PMC5243809.
  14. Takahashi T, Tagami T, Yamazaki S, Uede T, Shimizu J, Sakaguchi N, Mak TW, Sakaguchi S. Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J Exp Med. 2000 Jul 17;192(2):303-10. doi: 10.1084/jem.192.2.303. PMID: 10899917; PMCID: PMC2193248.
  15. Taves MD, Ashwell JD. Glucocorticoids in T cell development, differentiation and function. Nat Rev Immunol. 2021 Apr;21(4):233-243. Epub 2020 Nov 4. doi: 10.1038/s41577-020-00464-0. PMID: 33149283.
  16. 7. Thiault N, Darrigues J, Adoue V, Gros M, Binet B, Perals C, Leobon B, Fazilleau N, Joffre OP, Robey EA, van Meerwijk JP, Romagnoli P. Peripheral regulatory T lymphocytes recirculating to the thymus suppress the development of their precursors. Nat Immunol. 2015 Jun;16(6):628-34. Epub 2015 May 4. doi: 10.1038/ni.3150. PMID: 25939024.
  17. 8. Wildin RS, Ramsdell F, Peake J, Faravelli F, Casanova JL, Buist N, Levy-Lahad E, Mazzella M, Goulet O, Perroni L, Bricarelli FD, Byrne G, McEuen M, Proll S, Appleby M, Brunkow ME. X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat Genet. 2001 Jan;27(1):18-20. doi: 10.1038/83707. PMID: 11137992.

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Copyright (c) Abramova T.Y., Boeva O.S., Angelskaya O.A., Borisevich V.I., Abbasova V.S., Korolev M.A., Omelchenko V.O., Kurochkina Y.D., Rybakova A.D., Blinova E.A.

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