{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T03:33:23Z","timestamp":1793158403580,"version":"4.5.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T00:00:00Z","timestamp":1677110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Gut microbiota have been linked to modulating susceptibility to Type 1 diabetes; however, there are many ways in which the microbiota interact with host cells, including through microbial ligand binding to intracellular inflammasomes (large multi-subunit proteins) to initiate immune responses. NLRP6, a microbe-recognizing inflammasome protein, is highly expressed by intestinal epithelial cells and can alter susceptibility to cancer, obesity and Crohn\u2019s disease; however, the role of NLRP6 in modulating susceptibility to autoimmune diabetes, was previously unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We generated NLRP6-deficient Non-obese diabetic (NOD) mice to study the effect of NLRP6-deficiency on the immune cells and susceptibility to Type 1 diabetes development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>NLRP6-deficient mice exhibited an expansion of CD103<jats:sup>+<\/jats:sup> B cells and were protected from type 1 diabetes.  Moreover, NLRP6-deficient CD103<jats:sup>+<\/jats:sup> B cells express regulatory markers, secreted higher concentrations of IL-10 and TGFb1 cytokines and suppressed diabetogenic T cell proliferation, compared to NLRP6-sufficient CD103<jats:sup>+<\/jats:sup> B cells.  Microarray analysis of NLRP6-sufficient and -deficient CD103<jats:sup>+<\/jats:sup> B cells identified 79 significantly different genes including genes regulated by lipopolysaccharide (LPS), tretinoin, IL-10 and TGFb, which was confirmed in vitro following LPS stimulation.  Furthermore, microbiota from NLRP6-deficient mice induced CD103<jats:sup>+<\/jats:sup> B cells in colonized NLRP6-sufficient germ-free mice; however, the long-term maintenance of the CD103<jats:sup>+<\/jats:sup> B cells required the absence of NLRP6 in the hosts, or continued exposure to microbiota from NLRP6-deficient mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Together, our data indicate that NLRP6 deficiency promotes expansion and maintenance of a novel TGF -dependent CD103<jats:sup>+<\/jats:sup> Breg population. Thus, targeting NLRP6 therapeutically may prove clinically useful.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1147925","type":"journal-article","created":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T07:08:33Z","timestamp":1677136113000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["NLRP6 deficiency expands a novel CD103+ B cell population that confers immune tolerance in NOD mice"],"prefix":"10.3389","volume":"14","author":[{"given":"James A.","family":"Pearson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningwen","family":"Tai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youjia","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sha","family":"Sha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Flavell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. 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