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Mucosal barriers recruit more CCR6+ B cells and have higher immunogloblin A (IgA) Ab levels during normal, infectious, and inflammatory states. Ig isotypes at the mucosal surface are pivotal in modulating inflammatory responses and controlling infections. However, the intrinsic signaling pathway mediated by CCR6-CCL20 in B cells\u2014in particular, its impact on Ig isotype expression\u2014remains insufficiently investigated. In this study, the dextran sodium sulfate (DSS)\u2013induced gut inflammation model in C57BL\/6 mice was used. Our findings indicate that DSS administration elevates CCL20 production in the gut epithelium, which, in turn, enhances the differentiation of IgA+ B cells in gut-associated lymphoid tissues, while concurrently reducing both IgG1+ B-cell populations and serum IgG1 levels, in a CCR6-dependent manner. Furthermore, stimulation with CCL20 through CCR6 induces phosphorylation of the AKT\/mTOR\/STAT3 signaling pathways in B cells. Pharmacological inhibition of mTOR signaling with rapamycin effectively abrogated CCL20-driven differentiation of IgA+ B cells. Collectively, these results suggest a significant role for CCR6-CCL20 signaling, alongside other costimulatory mechanisms, in regulating Ig isotype switching at the mucosal barrier during intestinal inflammation, thereby offering important insights into CCR6-mediated inflammatory pathologies.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag150","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T23:26:31Z","timestamp":1781738791000},"source":"Crossref","is-referenced-by-count":0,"title":["CCR6-CCL20 signaling modulates immunoglobulin isotype switching at the mucosal barrier during gut inflammation"],"prefix":"10.1093","volume":"215","author":[{"given":"Priyanka D","family":"Padghan","sequence":"first","affiliation":[{"name":"Biotechnology Research and Innovation Council (BRIC)\u2013National Centre for Cell Science, Savitribai Phule Pune University Campus , Pune, Maharashtra,","place":["India"]},{"name":"Department of Biotechnology, Savitribai Phule Pune University , Pune, Maharashtra,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manisha","family":"Pathak","sequence":"additional","affiliation":[{"name":"Biotechnology Research and Innovation Council (BRIC)\u2013National Centre for Cell Science, Savitribai Phule Pune University Campus , Pune, Maharashtra,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3799-3603","authenticated-orcid":false,"given":"Girdhari","family":"Lal","sequence":"additional","affiliation":[{"name":"Biotechnology Research and Innovation Council (BRIC)\u2013National Centre for Cell Science, Savitribai Phule Pune University Campus , Pune, Maharashtra,","place":["India"]},{"name":"Department of Biotechnology, Savitribai Phule Pune University , Pune, Maharashtra,","place":["India"]},{"name":"Regional Centre for Biotechnology , Faridabad, 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