Date: Monday, November 9, 2020
Session Type: Abstract Session
Session Time: 10:00AM-10:50AM
Background/Purpose: Resident memory T cells (TRM) are site-specific memory T cells that take up long-term residence in peripheral tissues and aid in local immune defense. TRM have also been implicated in autoimmune diseases by driving localized recurrent inflammation. As chronic arthritis is characterized by recurrent site-specific joint inflammation, we sought to investigate the role of TRM in joint-specific memory.
Methods: We performed 10x genomics droplet-based single cell RNA sequencing and immune repertoire profiling on memory T cells disaggregated from human rheumatoid arthritis synovium to evaluate transcriptomic signature. We also used Mantra multispectral immunofluorescence microscopy to evaluate T cells expressing common TRM protein markers in human arthritic synovial tissue sections. To assess the functional contribution of TRM cells in arthritis in vivo, we generated a novel murine model of joint-specific recurrent synovitis. We utilized adoptive transfer, in vitro metabolic and migration assays, in vivo cell labeling, and localized depletion strategies to characterize TRM cells in the synovium and their functional role in arthritis flare.
Results: We identified cells with the phenotypic and transcriptomic signature of TRM within human arthritic synovium. These cells were primarily CD8+ and exhibited restricted T cell receptor clonotypes as well as a pro-inflammatory gene expression profile. Adoptive transfer studies in our animal model of joint-specific recurrent inflammation confirmed that arthritis flares were mediated by antigen-specific CD8+ T cells that remained within previously inflamed joints during remission. These cells were bona fide TRM, as confirmed through surface signature, failure to migrate in vivo or in vitro, preferential uptake of free fatty acids, and long-term residency. Site-specific depletion of synovial T cells during remission markedly ameliorated disease recurrence, establishing a role of synovial TRM in arthritis flares.
Conclusion: Here, we demonstrate that synovial TRM present in human inflamed synovium are a targetable mediator of joint-specific memory in arthritis.
To cite this abstract in AMA style:Chang M, Levescot A, Nelson-Maney N, Blaustein R, Winden K, Morris A, Balu S, Wactor A, Grieshaber-Bouyer R, Wei K, Henderson L, Clark R, Rao D, Fuhlbrigge R, Nigrovic P. Resident Memory T Cells in Synovial Tissue Mediate Arthritis Flares [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/resident-memory-t-cells-in-synovial-tissue-mediate-arthritis-flares/. Accessed November 25, 2020.
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