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T cell-Macrophage Interactions Mediate Innate and Adaptive Immune Responses in Histidyl-tRNA Synthetase-Induced Myositis

ABSTRACT: The relative contribution of innate and adaptive immunity to idiopathic inflammatory myopathy is poorly defined. We therefore sought to clarify these components of disease pathogenesis using our novel murine model of histidyl-tRNA synthetase (HRS)-induced myositis. Myositis was induced in WT and various congenic strains of C57BL/6 mice through intramuscular immunization with recombinant HRS. Histopathological, immunohistochemical, flow cytometric, and transcriptomic assessments were used to characterize muscle-infiltrating cell populations in these congenic strains. RAG1 KO mice developed markedly reduced muscle inflammation relative to WT mice, demonstrating a key requirement for T cells in driving HRS-induced myositis. Diminished cellular infiltration in CD4-Cre.MyD88fl/fl conditional knockout and OT-II TCR transgenic mice highlighted roles for innate and TCR-mediated/adaptive immune signaling in T cells. Transcriptionally-based pathway analyses showed that disruption of T cell signaling alters the function of macrophages, fibroblasts, and other non-lymphoid cell populations. Overall, these findings demonstrate that HRS-induced myositis reflects complex cellular interactions requiring the activation of both innate and adaptive T cell-mediated signaling pathways.

ORGANISM(S): Mus musculus

PROVIDER: GSE229059 | GEO | 2023/10/18

REPOSITORIES: GEO

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T cell-Macrophage Interactions Mediate Innate and Adaptive Immune Responses in Histidyl-tRNA Synthetase-Induced Myositis

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