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B cell-specific contributions of Bruton’s tyrosine kinase (BTK) in autoimmune arthritis 4196

Year: 2025
Type: article
Abstract: Description BTK is a signaling protein found in innate and B cells. Previously our lab has showed that BTK deficiency selectively eliminates autoreactive B cells and provides protection against autoimmune arthritis. However, whether these outcomes are intrinsic to B cells has not been investigated. B cell-specific KO mice were developed in the K/BxN model to test the hypothesis that BTK in non-B cells contributes to arthritis-related outcomes independently of its functions in B cells. Btkfl/y/Mb1-Cre K/BxN mice were paw-scored and after 10 weeks, mice were sacrificed, spleens and popliteal lymph nodes were used for studying adaptive and innate immune cell populations. Btkfl/y/Mb1-Cre K/BxN mice exhibited partial protection from arthritis compared to Fl+/y/KBxN mice, without reaching the level of protection found in global BTK-KO K/BxN mice. Flow cytometry analysis showed significant reductions in B cells, T cells, Treg, Dendritic, and macrophages in B cell-specific KO mice compared to Fl+/y/KBxN mice, similar to findings in global BTK deficiency. The observed partial protection from rheumatoid arthritis in B cell-specific KO mice suggests that BTK does have a role in supporting myeloid cell contributions to arthritis. The downregulation of T and myeloid cell components indicates that the absence of BTK in B cells has a broader impact on other immune counterparts than expected, highlighting the complexity of autoimmune diseases and emphasizing the need for further research in this area. Funding Sources National Institutes of Health Grants R01-DK-084246 Veteran’s Affairs I01-BX-002882 Washington University School of Medicine Topic Categories Basic Autoimmunity (BA)
DOI: 10.1093/jimmun/vkaf283.1909
Authors: Sonam Verma, Wumei Blanche, Amber Simone, Griffith Neil, Peggy L. Kendall
Language: English
Subfield: Rheumatology
Field: Medicine
Open Access status: bronze
OpenAlex ID: W4416450951
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