Arthritis flares mediated by tissue-resident memory T cells in the joint

Chang MH, Levescot A, Nelson-Maney N, Blaustein RB, Winden KD, Morris A, Wactor A, Balu S, Grieshaber-Bouyer R, Wei K, Henderson LA, Iwakura Y, Clark RA, Rao DA, Fuhlbrigge RC, Nigrovic PA (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Cell Reports Elsevier (Cell Press)

Book Volume: 37

Article Number: 109902

Journal Issue: 4

DOI: 10.1016/j.celrep.2021.109902

Abstract

Rheumatoid arthritis is a systemic autoimmune disease, but disease flares typically affect only a subset of joints, distributed in a distinctive pattern for each patient. Pursuing this intriguing pattern, we show that arthritis recurrence is mediated by long-lived synovial resident memory T cells (TRM). In three murine models, CD8+ cells bearing TRM markers remain in previously inflamed joints during remission. These cells are bona fide TRM, exhibiting a failure to migrate between joints, preferential uptake of fatty acids, and long-term residency. Disease flares result from TRM activation by antigen, leading to CCL5-mediated recruitment of circulating effector cells. Correspondingly, TRM depletion ameliorates recurrence in a site-specific manner. Human rheumatoid arthritis joint tissues contain a comparable CD8+-predominant TRM population, which is most evident in late-stage leukocyte-poor synovium, exhibiting limited T cell receptor diversity and a pro-inflammatory transcriptomic signature. Together, these findings establish synovial TRM as a targetable mediator of disease chronicity in autoimmune arthritis.

Authors with CRIS profile

Ricardo Grieshaber Bouyer

Involved external institutions

Boston Children's Hospital US United States (USA) (US) Brigham and Women's Hospital (BWH) US United States (USA) (US) Tokyo University of Science / 東京理科大学 (Tōkyō Rika Daigaku) JP Japan (JP) University of Colorado Anschutz Medical Campus US United States (USA) (US)

How to cite

APA:

Chang, M.H., Levescot, A., Nelson-Maney, N., Blaustein, R.B., Winden, K.D., Morris, A.,... Nigrovic, P.A. (2021). Arthritis flares mediated by tissue-resident memory T cells in the joint. Cell Reports, 37(4). https://doi.org/10.1016/j.celrep.2021.109902

MLA:

Chang, Margaret H., et al. "Arthritis flares mediated by tissue-resident memory T cells in the joint." Cell Reports 37.4 (2021).

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