In humans and mice, mucosal immune responses are dominated by IgA antibodies and the cytokine TGF‐β, suppressing unwanted immune reactions but also targeting Ig class switching to IgA. It had been suggested that eosinophils promote the generation and maintenance of mucosal IgA‐expressing plasma cells. Here, we demonstrate that not eosinophils, but specific bacteria determine mucosal IgA production. Co‐housing of eosinophil‐deficient mice with mice having high intestinal IgA levels, as well as the intentional microbiota transfer induces TGF‐β expression in intestinal T follicular helper cells, thereby promoting IgA class switching in Peyer's patches, enhancing IgA+ plasma cell numbers in the small intestinal lamina propria and levels of mucosal IgA. We show that bacteria highly enriched for the genus Anaeroplasma are sufficient to induce these changes and enhance IgA levels when adoptively transferred. Thus, specific members of the intestinal microbiota and not the microbiota as such regulate gut homeostasis, by promoting the expression of immune‐regulatory TGF‐β and of mucosal IgA.

Career situation of first and presenting authorPost-doctoral fellow.IntroductionThe human intestine is colonized with billions of microorganisms, which form the gut microbiota, consisting of up to 1000 different bacterial species. Recent studies have implicated the intestinal microbiota in the pathogenesis of chronic inflammatory diseases, such as rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, systemic sclerosis, and Sjögren’s syndrome. Yet, we still lack the knowledge which bacteria of the gut microbiota induce, promote or inhibit chronic inflammatory inflammation.ObjectivesThe aim of our work is to identify members of the intestinal microbiota with pro- or anti-inflammatory properties for targeted and therapeutic manipulation of the microbiota in chronic inflammatory diseases.MethodsWe have developed high-resolution microbiota flow cytometry which allows us to analyze the microbiota on a single cell level. This provides a non-invasive, fast and efficient diagnostic tool to visualize dramatic changes of microbiota composition in inflammatory diseases, fast and efficiently, and isolate distinct bacteria for functional and molecular analyses.ResultsWe have identified bacteria belonging to the genus Anaeroplasma, which enhances the levels of mucosal IgA. Adoptive transfer of Anaeroplasma increases the numbers of IgA+ germinal center B cells in the Peyer’s patches and of IgA-secreting plasma cells in the lamina propria of the small intestine leading to significantly enhanced mucosal IgA levels. Anaeroplasma controls IgA expression presumably its ability to induce expression of the regulatory cytokine TGF-β in T cells, as we show here.ConclusionsThe anti-inflammatory properties of Anaeroplasma to induce the anti-inflammatory cytokine TGF-β, thereby also strengthening the intestinal barrier by enhancing mucosal IgA, qualify Anaeroplasma as potent probiotic for the prevention and treatment of chronic inflammation.Disclosure of InterestNone declared.