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

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...

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Autores principales: Bonami, Rachel H., Thurman, Christina E., Verma, Sonam, Westlake, Camille S., Nyhoff, Lindsay E., Barron, Bridgette B., Reboldi, Andrea, Kendall, Peggy L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9002138/
https://www.ncbi.nlm.nih.gov/pubmed/35422819
http://dx.doi.org/10.3389/fimmu.2022.748284
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author Bonami, Rachel H.
Thurman, Christina E.
Verma, Sonam
Westlake, Camille S.
Nyhoff, Lindsay E.
Barron, Bridgette B.
Reboldi, Andrea
Kendall, Peggy L.
author_facet Bonami, Rachel H.
Thurman, Christina E.
Verma, Sonam
Westlake, Camille S.
Nyhoff, Lindsay E.
Barron, Bridgette B.
Reboldi, Andrea
Kendall, Peggy L.
author_sort Bonami, Rachel H.
collection PubMed
description 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.
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spelling pubmed-90021382022-04-13 Bruton’s Tyrosine Kinase Supports Gut Mucosal Immunity and Commensal Microbiome Recognition in Autoimmune Arthritis Bonami, Rachel H. Thurman, Christina E. Verma, Sonam Westlake, Camille S. Nyhoff, Lindsay E. Barron, Bridgette B. Reboldi, Andrea Kendall, Peggy L. Front Immunol Immunology 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. Frontiers Media S.A. 2022-03-29 /pmc/articles/PMC9002138/ /pubmed/35422819 http://dx.doi.org/10.3389/fimmu.2022.748284 Text en Copyright © 2022 Bonami, Thurman, Verma, Westlake, Nyhoff, Barron, Reboldi and Kendall https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Bonami, Rachel H.
Thurman, Christina E.
Verma, Sonam
Westlake, Camille S.
Nyhoff, Lindsay E.
Barron, Bridgette B.
Reboldi, Andrea
Kendall, Peggy L.
Bruton’s Tyrosine Kinase Supports Gut Mucosal Immunity and Commensal Microbiome Recognition in Autoimmune Arthritis
title Bruton’s Tyrosine Kinase Supports Gut Mucosal Immunity and Commensal Microbiome Recognition in Autoimmune Arthritis
title_full Bruton’s Tyrosine Kinase Supports Gut Mucosal Immunity and Commensal Microbiome Recognition in Autoimmune Arthritis
title_fullStr Bruton’s Tyrosine Kinase Supports Gut Mucosal Immunity and Commensal Microbiome Recognition in Autoimmune Arthritis
title_full_unstemmed Bruton’s Tyrosine Kinase Supports Gut Mucosal Immunity and Commensal Microbiome Recognition in Autoimmune Arthritis
title_short Bruton’s Tyrosine Kinase Supports Gut Mucosal Immunity and Commensal Microbiome Recognition in Autoimmune Arthritis
title_sort bruton’s tyrosine kinase supports gut mucosal immunity and commensal microbiome recognition in autoimmune arthritis
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9002138/
https://www.ncbi.nlm.nih.gov/pubmed/35422819
http://dx.doi.org/10.3389/fimmu.2022.748284
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