Arthritis Flares Mediated by Tissue Resident Memory T Cells in the Joint
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ABSTRACT:
PROVIDER: PRJNA765299 | ENA |
REPOSITORIES: ENA
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Project description:Rheumatoid arthritis is a systemic autoimmune disease, but disease flares typically affect only a subset of joints, distributed in a pattern that is distinctive 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 failure to migrate from joint to joint, 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, 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 cells as a targetable mediator of disease chronicity in autoimmune arthritis.
2021-09-23 | GSE184582 | GEO
Project description:Interleukin (IL)-17A plays a central role in driving joint pathology in Spondyloarthritis (SpA). In this study, synovial tissues from patients with Axial SpA and Psoriatic arthritis were analyzed using single-cell RNA sequencing and spatial RNA profiling to pinpoint the cellular source of IL-17A. The results revealed that IL-17A expression is exclusively localized to CD4⁺CXCR6⁺ tissue resident memory Th17 (TRM17) cells, which interact with activated CLEC10A⁺ dendritic cells within the joint. These interactions coincide with an enhanced IL-17A response signature in both sublining and lining fibroblasts. Furthermore, in vitro-generated TRM17-like cells from blood memory CD4⁺ T cells recapitulated the in situ characteristics by producing IL-17A in response to T cell receptor stimulation, while IL-23 selectively amplified TCR-mediated IL-17F and IFN-γ production. Importantly, perturbation of the epigenetic regulator BRD1 impaired the generation of TRM17-like cells. These findings underscore the predominant role of TRM17 cells as the source of IL-17A in SpA and suggest that targeting BRD1 or depleting TRM17 cells may offer promising therapeutic strategies for achieving long-term disease remission.
2025-05-29 | GSE290921 | GEO
Project description:CD4+ tissue resident memory Th17 cells drive IL-17A-mediated joint pathology in Spondyloarthritis
| PRJNA1230879 | ENA
Project description:CD8 Tissue Resident Memory (TRM) induction
| PRJNA1036221 | ENA
Project description:Previously, using a forward genetic approach we identified B. burgdorferi arthritis-associated locus 1 (Bbaa1), a quantitative trait locus on Chr4, which physically encompasses the type I IFN gene cluster and regulates Lyme arthritis through heightened type I IFN production. Reciprocal radiation chimeras between B6.C3-Bbaa1 and B6 mice revealed that arthritis is initiated by radiation-sensitive cells, but orchestrated by radiation-resistant components of joint tissue. Advanced congenic lines were developed to reduce the physical size of the Bbaa1 interval, and RNA-seq of resident CD45- joint cells from advanced interval specific recombinant congenic lines (ISRCL4 and ISRCL3) identified myostatin as uniquely upregulated in association with Bbaa1 arthritis development. Our manuscript further demonstrates that myostatin expression is linked to IFN-β production, and in vivo inhibition of myostatin suppresses Lyme arthritis in the reduced interval Bbaa1 congenic mice, formally implicating myostatin as a novel downstream mediator of joint-specific inflammatory response to B. burgdorferi.
2018-02-13 | GSE102748 | GEO
Project description:Transcriptomic analysis for temporomandibular joint arthritis
| PRJNA1225221 | ENA
Project description:Macrophages (MΦs) are considered to contribute to chronic inflammatory diseases such as rheumatoid arthritis 1. However, both the exact origin and role of MΦs during inflammatory joint disease remain unclear. Here, we used multiple fate-mapping approaches in conjunction with 3D-light-sheet fluorescence microscopy and single cell RNA sequencing to perform a comprehensive spatiotemporal analysis of the composition, origin and differentiation of MΦ subsets within the healthy and inflamed joint and subsequently studied their roles during arthritis. This approach revealed dynamic membrane-like structures consisting of a distinct population of CX3CR1+ tissue-resident MΦs that formed an internal immunological barrier at the synovial lining and physically secluded the joint. Barrier-forming MΦs displayed features otherwise typical of epithelial cells, and maintained their numbers through a pool of locally proliferating CX3CR1- mononuclear cells embedded into the synovial tissue. Unlike recruited monocyte-derived MΦs, which actively contributed to joint inflammation, such epithelial-like CX3CR1+ lining MΦs restricted the inflammatory reaction by providing a tight junction-mediated shield for intra-articular structures. Our data thus reveal an unexpected functional diversification among synovial MΦs and have important implications for the general role of MΦs in health and disease
2019-08-07 | GSE134420 | GEO
Project description:Macrophages (MΦs) are considered to contribute to chronic inflammatory diseases such as rheumatoid arthritis 1. However, both the exact origin and role of MΦs during inflammatory joint disease remain unclear. Here, we used multiple fate-mapping approaches in conjunction with 3D-light-sheet fluorescence microscopy and single cell RNA sequencing to perform a comprehensive spatiotemporal analysis of the composition, origin and differentiation of MΦ subsets within the healthy and inflamed joint and subsequently studied their roles during arthritis. This approach revealed dynamic membrane-like structures consisting of a distinct population of CX3CR1+ tissue-resident MΦs that formed an internal immunological barrier at the synovial lining and physically secluded the joint. Barrier-forming MΦs displayed features otherwise typical of epithelial cells, and maintained their numbers through a pool of locally proliferating CX3CR1- mononuclear cells embedded into the synovial tissue. Unlike recruited monocyte-derived MΦs, which actively contributed to joint inflammation, such epithelial-like CX3CR1+ lining MΦs restricted the inflammatory reaction by providing a tight junction-mediated shield for intra-articular structures. Our data thus reveal an unexpected functional diversification among synovial MΦs and have important implications for the general role of MΦs in health and disease.
2019-08-07 | GSE134286 | GEO
Project description: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.
| S-EPMC8561718 | biostudies-literature
Project description:Comparison of the transcriptional profiles of full-thickness murine skin harboring tissue resident memory T cells exposed to specific or control trigger Expression profiling by high throughput sequencing
2014-09-11 | E-GEOD-60599 | biostudies-arrayexpress