Specific microbiota enhances intestinal IgA levels by inducing TGF-β in T follicular helper cells of Peyer's patches in mice
Open Access
- 1 June 2020
- journal article
- research article
- Published by Wiley in European Journal of Immunology
- Vol. 50 (6), 783-794
- https://doi.org/10.1002/eji.201948474
Abstract
In humans and mice, mucosal immune responses are dominated by IgA antibodies and the cytokine TGF-beta, 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-beta 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-beta and of mucosal IgA.Funding Information
- Russian Science Foundation (17‐74‐20059)
- Deutsche Forschungsgemeinschaft (SFB TRR130, SPP1656, TRR241)
- Leibniz-Gemeinschaft
- H2020 Marie Skłodowska-Curie Actions
This publication has 45 references indexed in Scilit:
- phyloseq: An R Package for Reproducible Interactive Analysis and Graphics of Microbiome Census DataPLOS ONE, 2013
- Follicular Helper CD4 T Cells (TFH)Annual Review of Immunology, 2011
- Enteric defensins are essential regulators of intestinal microbial ecologyNature Immunology, 2009
- A T Cell-Dependent Mechanism for the Induction of Human Mucosal Homing Immunoglobulin A-Secreting PlasmablastsImmunity, 2009
- TGF-β: A Master of All T Cell TradesCell, 2008
- Dendritic Cells from Peyer’s Patches and Mesenteric Lymph Nodes Differ from Spleen Dendritic Cells in their Response to Commensal Gut BacteriaScandinavian Journal of Immunology, 2008
- Naïve Bayesian Classifier for Rapid Assignment of rRNA Sequences into the New Bacterial TaxonomyApplied and Environmental Microbiology, 2007
- Generation of Gut-Homing IgA-Secreting B Cells by Intestinal Dendritic CellsScience, 2006
- Smad and AML Proteins Synergistically Confer Transforming Growth Factor β1 Responsiveness to Human Germ-line IgA GenesOnline Journal of Public Health Informatics, 2000
- Switch Transcripts in Immunoglobulin Class SwitchingScience, 1995