Year: 2021
Type: article
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 (T RM ). In three murine models, CD8+ cells bearing T RM markers remain in previously inflamed joints during remission. These cells are bona fide T RM , exhibiting a failure to migrate between joints, preferential uptake of fatty acids, and long-term residency. Disease flares result from T RM activation by antigen, leading to CCL5-mediated recruitment of circulating effector cells. Correspondingly, T RM depletion ameliorates recurrence in a site-specific manner. Human rheumatoid arthritis joint tissues contain a comparable CD8+-predominant T RM 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 T RM as a targetable mediator of disease chronicity in autoimmune arthritis.
Source: Cell Reports
Authors: Margaret H. Chang, Anaïs Levescot, Nathan Nelson-Maney, Rachel B. Blaustein, Kellen D. Winden, Allyn Morris, Alexandra Wactor, Spoorthi Balu, Ricardo Grieshaber-Bouyer, Kevin Wei, Lauren A. Henderson, Yoichiro Iwakura, Rachael A. Clark, Deepak A. Rao, Robert C. Fuhlbrigge, Peter A. Nigrovic
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,200
Funders: Burroughs Wellcome Fund, American College of Rheumatology Research and Education Foundation, Arthritis National Research Foundation, Gilead Sciences, Rheumatology Research Foundation, Fundación Bechara, National Research Foundation, Boehringer Ingelheim Fonds, National Institutes of Health, Japan Society for the Promotion of Science, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: The Reprogramming of Regulatory T cells to a Th17 Phenotype in Systemic Juvenile Idiopathic Arthritis, Generation of gene-modified mice by targeting on innate immune receptor family and analysis of the function of these receptors by using human disease-models., Institutional Career Development Core, G2460837612, Molecular Mechanisms of Neuronal Hyperactivity in Tuberous Sclerosis Complex, Ly6 family members in neutrophil biology, T resident memory cells in arthritis, Reversing immune evasion and enhancing immune detection with topical resiquimod, Transforming the diagnosis and care of patients with CTCL using TCR sequencing, Pathogenic fibroblast differentiation in rheumatoid arthritis, Generation of Robust Resident Memory T cells in Barrier Tissues through Skin Vaccination, Modulation of neutrophil function through emperipolesis, Impact of emperipolesis on platelet function, G7591972029, Boston Children's Hospital/HMS Intellectual and Developmental Disabilities Research Center, Molecular Basis of Allergic and Immunologic Disease, Joint Biology Consortium Resource-based Center, Child Health Research Career Development Award (CHRCDA) Program (K12), Human Skin Disease Resource-based Center, Bridging the gap between GWAS and mechanism in arthritis
OpenAlex ID: W3166784399