Bruton's Tyrosine Kinase Supports Gut Mucosal Immunity and Commensal Microbiome Recognition in Autoimmune Arthritis.

Autor:	Bonami RH; Department of Medicine, Division of Rheumatology and Immunology, Vanderbilt University Medical Center, Nashville, TN, United States.; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, United States.; Vanderbilt Institute for Infection, Immunology, and Inflammation (VI4), Nashville, TN, United States., Thurman CE; Department of Medicine, Division of Allergy, Pulmonary, and Critical Care, Vanderbilt University Medical Center, Nashville, TN, United States., Verma S; Department of Medicine, Division of Allergy and Immunology, Washington University School of Medicine, St. Louis, MO, United States., Westlake CS; Department of Medicine, Division of Allergy, Pulmonary, and Critical Care, Vanderbilt University Medical Center, Nashville, TN, United States., Nyhoff LE; Department of Medicine, Division of Allergy, Pulmonary, and Critical Care, Vanderbilt University Medical Center, Nashville, TN, United States., Barron BB; Department of Medicine, Division of Allergy, Pulmonary, and Critical Care, Vanderbilt University Medical Center, Nashville, TN, United States., Reboldi A; Department of Pathology, University of Massachusetts Chan Medical School, Worcester, MA, United States., Kendall PL; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, United States.; Vanderbilt Institute for Infection, Immunology, and Inflammation (VI4), Nashville, TN, United States.; Department of Medicine, Division of Allergy, Pulmonary, and Critical Care, Vanderbilt University Medical Center, Nashville, TN, United States.; Department of Medicine, Division of Allergy and Immunology, Washington University School of Medicine, St. Louis, MO, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Mar 29; Vol. 13, pp. 748284. Date of Electronic Publication: 2022 Mar 29 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.748284
Abstrakt:	Bruton's tyrosine kinase ( Btk ) deficiency preferentially eliminates autoreactive B cells while sparing normal humoral responses, but has not been studied in mucosal immunity. Commensal microbes and intact BTK signaling have been independently shown to be essential for arthritis development in K/BxN mice. Here, we examine how BTK-mediated signaling interfaces with the gut microbiome. Btk -deficient K/BxN mice were found to have small Peyer's Patches with reduced germinal center and IgA class-switched B cells. IgA-switched plasma cells in small intestines were reduced, especially in villi of Btk -deficient mice. IgH CDR3 sequencing showed similar V gene diversity and somatic hypermutation frequency despite Btk deficiency but showed reduced CDR3 amino acid polarity, suggesting potential qualitative differences in the gut plasma cell repertoire. Small intestinal IgA was low and IgA coating of commensal bacteria was reduced. IgA-seq showed a shift in small intestinal microbes that are normally IgA-coated into the uncoated fraction in Btk -deficient mice. Overall, this study shows that BTK supports normal intestinal IgA development in response to commensals. This manuscript was previously published as a preprint at: https://www.biorxiv.org/content/10.1101/2021.03.10.434762v2. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Bonami, Thurman, Verma, Westlake, Nyhoff, Barron, Reboldi and Kendall.)
Databáze:	MEDLINE
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