{"doi":"10.1101/2021.03.10.434762","title":"Bruton’s Tyrosine Kinase Supports Gut Mucosal Immunity and Commensal Microbiome Recognition in Autoimmune Arthritis","abstract":"Abstract 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 are essential for arthritis in K/BxN mice, used here to examine how BTK-mediated signaling interfaces with the microbiome. Btk -deficient K/BxN mice were found to have small Peyer’s Patches with reduced germinal center and IgA + B cells. Although lamina propria IgA + plasma cells were numerically normal, intestinal IgA was low and IgA coating of commensal bacteria was reduced. IgA-seq showed a shift in microbes that are normally IgA-coated into the uncoated fraction in Btk -deficient mice. In this altered microbial milieau, the proportion of Parabacteroides distasonis was reduced in Btk -deficient K/BxN mice. To determine whether P. distasonis contributes to arthritis, it was reintroduced into antibiotic-protected K/BxN mice, where it restored disease. This suggests that P. distasonis’ inability to thrive in Btk -deficient mice may be a factor in disease protection. Thus, BTK supports normal intestinal IgA development, with downstream effects on the microbiome that may contribute to autoimmunity.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":220327,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9536,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":820207,"name":"Christina E. Thurman","orcid":null,"position":1,"is_corresponding":false},{"id":707551,"name":"Camille S. Westlake","orcid":"0000-0001-7847-8643","position":2,"is_corresponding":false},{"id":226155,"name":"Lindsay E. Nyhoff","orcid":"0000-0001-5767-6122","position":3,"is_corresponding":false},{"id":820208,"name":"Bridgette B. Barron","orcid":null,"position":4,"is_corresponding":false},{"id":280632,"name":"Peggy L. Kendall","orcid":"0000-0002-0516-654X","position":5,"is_corresponding":false},{"id":428126,"name":"Rachel H. Bonami","orcid":"0000-0001-7575-6943","position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":null,"created_at":"2026-07-18T23:53:46.965811Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}