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SRA promotes pathogenic Th17 response through inflammatory activation of M-MDSCs in autoimmune arthritis 2645

Year: 2025
Type: article
Abstract: Description Objectives We have identified the innate pattern recognition scavenger receptor A (SRA) and proinflammatory monocytic myeloid-derived suppressive cells (M-MDSCs) as critical factors involved in pathogenesis of rheumatoid arthritis (RA). Here we investigate the functional regulation of M-MDSCs by SRA in driving a pathogenic T helper 17 (Th17) response. Methods The M-MDSCs in wild-type (WT) or SRA knockout (SRA-/-) arthritic mice were characterized for their phenotypes and their capacity of pro-Th17 differentiation. The role of M-MDSCs in mediating SRA-facilitated Th17 response and disease pathology was examined by depletion or adoptive transfer of M-MDSCs. The SRA-dependent proinflammatory function of M-MDSCs and activation of the NLRP3-IL-1b immune axis was established using neutralizing antibodies or inhibitors. Results The presence of SRA on M-MDSCs defines their pro-inflammatory phenotype. The SRA loss impairs the NLRP3-depedent IL-1b production by M-MDSCs and their ability to potentiate Th17 polarization. Depletion of M-MDSCs abolishes the differences in disease severity in WT and SRA-/- mice. SRA blockade alleviates disease progression associated with attenuation of Th17 response in arthritic mice. Conclusions Our studies provide mechanistic insights into SRA-governed cellular and molecular inflammatory pathways involved in autoimmune arthritis. SRA-targeted therapies may provide new opportunities to manage RA in patients. Funding Sources US Department of Defense Award (W81XWH1910538) Virginia Commonwealth University (VCU) Massey Cancer Center Research Development Funds Topic Categories Therapeutic Approaches to Autoimmunity (THER)
DOI: 10.1093/jimmun/vkaf283.541
Language: English
Subfield: Rheumatology
Field: Medicine
Open Access status: bronze
OpenAlex ID: W4416449778
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