Academic Journal
Antigen-driven T cell-macrophage interactions mediate the interface between innate and adaptive immunity in histidyl-tRNA synthetase-induced myositis
| العنوان: | Antigen-driven T cell-macrophage interactions mediate the interface between innate and adaptive immunity in histidyl-tRNA synthetase-induced myositis |
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| المؤلفون: | Reay, Daniel P., Tabib, Tracy, Wang, Ying, Oriss, Timothy B., Young, Nicholas A., Lafyatis, Robert A., Jarjour, Wael N., Clemens, Paula R., Ascherman, Dana P. |
| المساهمون: | National Institutes of Health |
| المصدر: | Frontiers in Immunology ; volume 14 ; ISSN 1664-3224 |
| بيانات النشر: | Frontiers Media SA |
| سنة النشر: | 2023 |
| المجموعة: | Frontiers (Publisher - via CrossRef) |
| الوصف: | Introduction Previous work in humans has demonstrated that both innate and adaptive immune signaling pathways contribute to the pathogenesis of idiopathic inflammatory myopathy (IIM), a systemic autoimmune disease targeting muscle as well as extra-muscular organs. To better define interactive signaling networks in IIM, we characterized the cellular phenotype and transcriptomic profiles of muscle-infiltrating cells in our established murine model of histidyl-tRNA synthetase (HRS)-induced myositis. Methods Myositis was induced in wild type (WT) and various congenic/mutant strains of C57BL/6 mice through intramuscular immunization with recombinant HRS. Histopathological, immunohistochemical, flow cytometric, and transcriptomic assessments were used to characterize the functional relationship between muscle-infiltrating cell populations in these strains lacking different components of innate and/or adaptive immune signaling. Results RAG1 KO mice developed markedly reduced muscle inflammation relative to WT mice, demonstrating a key requirement for T cells in driving HRS-induced myositis. While the reduction of mononuclear cell infiltrates in CD4-Cre.MyD88fl/fl conditional knockout mice and OT-II TCR transgenic mice highlighted roles for both innate and TCR-mediated/adaptive immune signaling in T cells, diminished inflammation in Lyz2-Cre.MyD88fl/fl conditional knockout mice underscored the importance of macrophage/myeloid cell populations in supporting T cell infiltration. Single cell RNA sequencing-based clustering of muscle-infiltrating subpopulations and associated pathway analyses showed that perturbations of T cell signaling/function alter the distribution and phenotype of macrophages, fibroblasts, and other non-lymphoid cell populations contributing to HRS-induced myositis. Discussion Overall, HRS-induced myositis reflects the complex interplay between multiple cell types that collectively drive a TH1-predominant, pro-inflammatory tissue phenotype requiring antigen-mediated activation of both MyD88- and ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| DOI: | 10.3389/fimmu.2023.1238221 |
| DOI: | 10.3389/fimmu.2023.1238221/full |
| الاتاحة: | http://dx.doi.org/10.3389/fimmu.2023.1238221 https://www.frontiersin.org/articles/10.3389/fimmu.2023.1238221/full |
| Rights: | https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.BAF6BCCA |
| قاعدة البيانات: | BASE |
| DOI: | 10.3389/fimmu.2023.1238221 |
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