Specific microbiota enhances intestinal IgA levels by inducing TGF‐β in T follicular helper cells of Peyer's patches in mice

Beller, Alexander; Kruglov, Andrey; Durek, Pawel; von Goetze, Victoria; Werner, Katharina; Heinz, Gitta Anne; Ninnemann, Justus; Lehmann, Katrin; Maier, René; Hoffmann, Ute; Riedel, René; Heiking, Kevin; Zimmermann, Jakob; Siegmund, Britta; Mashreghi, Mir‐Farzin; Radbruch, Andreas; Chang, Hyun‐Dong (2020). Specific microbiota enhances intestinal IgA levels by inducing TGF‐β in T follicular helper cells of Peyer's patches in mice. European journal of immunology, 50(6), pp. 783-794. Wiley-VCH 10.1002/eji.201948474

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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 genera- tion 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Gastroenterology

UniBE Contributor:

Zimmermann, Jakob

Subjects:

500 Science > 570 Life sciences; biology

ISSN:

0014-2980

Publisher:

Wiley-VCH

Funders:

[103] European Commission FP7

Projects:

[UNSPECIFIED] 744257

Language:

English

Submitter:

Jakob Zimmermann

Date Deposited:

17 Jun 2020 17:26

Last Modified:

17 Jun 2020 17:26

Publisher DOI:

10.1002/eji.201948474

PubMed ID:

32065660

BORIS DOI:

10.7892/boris.144687

URI:

https://boris.unibe.ch/id/eprint/144687

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