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Mucosal Immunol. 2019 Jan;12(1):85-96. doi: 10.1038/s41385-018-0056-x. Epub 2018 Aug 7.

Defective IgA response to atypical intestinal commensals in IL-21 receptor deficiency reshapes immune cell homeostasis and mucosal immunity.

Author information

1
Mucosal Immunobiology Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA.
2
Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
3
Federal Institute of Parana, Palmas, Brazil.
4
Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, NIH, Bethesda, MD, USA.
5
Research Technologies Branch, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA.
6
Basic Science Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Fredrick, MD, USA.
7
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
8
Mucosal Immunobiology Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA. bkelsall@niaid.nih.gov.

Abstract

Despite studies indicating the effects of IL-21 signaling in intestinal inflammation, its roles in intestinal homeostasis and infection are not yet clear. Here, we report potent effects of commensal microbiota on the phenotypic manifestations of IL-21 receptor deficiency. IL-21 is produced highly in the small intestine and appears to be critical for mounting an IgA response against atypical commensals such as segmented filamentous bacteria and Helicobacter, but not to the majority of commensals. In the presence of these atypical commensals, IL-21R-deficient mice exhibit reduced numbers of germinal center and IgA+ B cells and expression of activation-induced cytidine deaminase in Peyer's patches as well as a significant decrease in small intestine IgA+ plasmablasts and plasma cells, leading to higher bacterial burdens and subsequent expansion of Th17 and Treg cells. These microbiota-mediated secondary changes in turn enhance T cell responses to an oral antigen and strikingly dampen Citrobacter rodentium-induced immunopathology, demonstrating a complex interplay between IL-21-mediated mucosal immunity, microbiota, and pathogens.

PMID:
30087442
PMCID:
PMC6301133
DOI:
10.1038/s41385-018-0056-x
[Indexed for MEDLINE]
Free PMC Article

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