Autoreactive Memory Th17 cells Are Principally Derived from T-betRORγt Th17/1 Effectors

Overview

Journal J Autoimmun

Specialty Allergy & Immunology

Date 2022 Apr 8

PMID 35395541

Authors

Nai-Wen Fan

Shudan Wang

Gustavo Ortiz

Sunil K Chauhan

Yihe Chen

Reza Dana

Affiliations

Soon will be listed here.

Abstract

Effector Th17 cells, including IFN-γIL-17 (eTh17) and IFN-γIL-17 (eTh17/1) subsets, play critical pathogenic functions in the induction of autoimmunity. As acute inflammation subsides, a small proportion of the effectors survive and convert to memory Th17 cells (mTh17), which sustain chronic inflammation in autoimmune diseases. Herein, we investigated the differential contributions of eTh17 versus eTh17/1 to the memory pool using an experimental model of ocular autoimmune disease. Our results show that adoptive transfer of Tbx21 CD4 T cells or conditional deletion of Tbx21 in Th17 cells leads to diminished eTh17/1 in acute phase and functionally compromised mTh17 in chronic phase. Further, adoptive transfer of disease-specific eTh17/1, but not eTh17, leads to generation of mTh17 and sustained ocular inflammation. Collectively, our data demonstrate that T-bet-dependent eTh17/1 cells generated during the acute inflammation are the principal effector precursors of pathogenic mTh17 cells that sustain the chronicity of autoimmune inflammation.

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References

Raphael I, Joern R, Forsthuber T . Memory CD4 T Cells in Immunity and Autoimmune Diseases. Cells. 2020; 9(3). PMC: 7140455. DOI: 10.3390/cells9030531. View

DuPage M, Bluestone J . Harnessing the plasticity of CD4(+) T cells to treat immune-mediated disease. Nat Rev Immunol. 2016; 16(3):149-63. DOI: 10.1038/nri.2015.18. View

Chen Y, Chauhan S, Tan X, Dana R . Interleukin-7 and -15 maintain pathogenic memory Th17 cells in autoimmunity. J Autoimmun. 2016; 77:96-103. PMC: 5276802. DOI: 10.1016/j.jaut.2016.11.003. View

Chen Y, Shao C, Fan N, Nakao T, Amouzegar A, Chauhan S . The functions of IL-23 and IL-2 on driving autoimmune effector T-helper 17 cells into the memory pool in dry eye disease. Mucosal Immunol. 2020; 14(1):177-186. PMC: 7581618. DOI: 10.1038/s41385-020-0289-3. View

Intlekofer A, Takemoto N, Wherry E, Longworth S, Northrup J, Palanivel V . Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin. Nat Immunol. 2005; 6(12):1236-44. DOI: 10.1038/ni1268. View

Annunziato F, Cosmi L, Santarlasci V, Maggi L, Liotta F, Mazzinghi B . Phenotypic and functional features of human Th17 cells. J Exp Med. 2007; 204(8):1849-61. PMC: 2118657. DOI: 10.1084/jem.20070663. View

Stern M, Schaumburg C, Siemasko K, Gao J, Wheeler L, Grupe D . Autoantibodies contribute to the immunopathogenesis of experimental dry eye disease. Invest Ophthalmol Vis Sci. 2012; 53(4):2062-75. PMC: 6713471. DOI: 10.1167/iovs.11-9299. View

Cosmi L, Maggi L, Santarlasci V, Liotta F, Annunziato F . T helper cells plasticity in inflammation. Cytometry A. 2013; 85(1):36-42. DOI: 10.1002/cyto.a.22348. View

Harrington L, Janowski K, Oliver J, Zajac A, Weaver C . Memory CD4 T cells emerge from effector T-cell progenitors. Nature. 2008; 452(7185):356-60. DOI: 10.1038/nature06672. View

10.

Ahmed R, Bevan M, Reiner S, Fearon D . The precursors of memory: models and controversies. Nat Rev Immunol. 2009; 9(9):662-8. DOI: 10.1038/nri2619. View

11.

Pepper M, Jenkins M . Origins of CD4(+) effector and central memory T cells. Nat Immunol. 2011; 12(6):467-71. PMC: 4212218. DOI: 10.1038/ni.2038. View

12.

Bazzazi H, Aghaei M, Memarian A, Asgarian-Omran H, Behnampour N, Yazdani Y . Th1-Th17 Ratio as a New Insight in Rheumatoid Arthritis Disease. Iran J Allergy Asthma Immunol. 2018; 17(1):68-77. View

13.

Frentsch M, Arbach O, Kirchhoff D, Moewes B, Worm M, Rothe M . Direct access to CD4+ T cells specific for defined antigens according to CD154 expression. Nat Med. 2005; 11(10):1118-24. DOI: 10.1038/nm1292. View

14.

Subbarayal B, Chauhan S, Di Zazzo A, Dana R . IL-17 Augments B Cell Activation in Ocular Surface Autoimmunity. J Immunol. 2016; 197(9):3464-3470. PMC: 5101134. DOI: 10.4049/jimmunol.1502641. View

15.

Hirota K, Duarte J, Veldhoen M, Hornsby E, Li Y, Cua D . Fate mapping of IL-17-producing T cells in inflammatory responses. Nat Immunol. 2011; 12(3):255-63. PMC: 3040235. DOI: 10.1038/ni.1993. View

16.

Lohning M, Hegazy A, Pinschewer D, Busse D, Lang K, Hofer T . Long-lived virus-reactive memory T cells generated from purified cytokine-secreting T helper type 1 and type 2 effectors. J Exp Med. 2008; 205(1):53-61. PMC: 2234365. DOI: 10.1084/jem.20071855. View

17.

Kirchhoff D, Frentsch M, Leclerk P, Bumann D, Rausch S, Hartmann S . Identification and isolation of murine antigen-reactive T cells according to CD154 expression. Eur J Immunol. 2007; 37(9):2370-7. DOI: 10.1002/eji.200737322. View

18.

Cosmi L, Santarlasci V, Maggi L, Liotta F, Annunziato F . Th17 plasticity: pathophysiology and treatment of chronic inflammatory disorders. Curr Opin Pharmacol. 2014; 17:12-6. DOI: 10.1016/j.coph.2014.06.004. View

19.

Lemp M . Report of the National Eye Institute/Industry workshop on Clinical Trials in Dry Eyes. CLAO J. 1995; 21(4):221-32. View

20.

Krausgruber T, Schiering C, Adelmann K, Harrison O, Chomka A, Pearson C . T-bet is a key modulator of IL-23-driven pathogenic CD4(+) T cell responses in the intestine. Nat Commun. 2016; 7:11627. PMC: 4874038. DOI: 10.1038/ncomms11627. View