Antigen-presenting ILC3 regulate T cell-dependent IgA responses to colonic mucosal bacteria.

The Journal of Experimental Medicine
Felipe Melo-GonzalezMatthew R Hepworth

Abstract

Intestinal immune homeostasis is dependent upon tightly regulated and dynamic host interactions with the commensal microbiota. Immunoglobulin A (IgA) produced by mucosal B cells dictates the composition of commensal bacteria residing within the intestine. While emerging evidence suggests the majority of IgA is produced innately and may be polyreactive, mucosal-dwelling species can also elicit IgA via T cell-dependent mechanisms. However, the mechanisms that modulate the magnitude and quality of T cell-dependent IgA responses remain incompletely understood. Here we demonstrate that group 3 innate lymphoid cells (ILC3) regulate steady state interactions between T follicular helper cells (TfH) and B cells to limit mucosal IgA responses. ILC3 used conserved migratory cues to establish residence within the interfollicular regions of the intestinal draining lymph nodes, where they act to limit TfH responses and B cell class switching through antigen presentation. The absence of ILC3-intrinsic antigen presentation resulted in increased and selective IgA coating of bacteria residing within the colonic mucosa. Together these findings implicate lymph node resident, antigen-presenting ILC3 as a critical regulatory checkpoint in the genera...Continue Reading

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Citations

Nov 20, 2019·Proceedings of the National Academy of Sciences of the United States of America·John W BostickLiang Zhou
Nov 30, 2019·Immunology·Stephanie C Ganal-Vonarburg, Claudia U Duerr
Jan 15, 2020·Mucosal Immunology·Dilini C GunasekeraJay H Bream
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Sep 12, 2019·Frontiers in Immunology·Tim Willinger
Sep 4, 2020·Cellular & Molecular Immunology·Jezabel VaradéÁfrica González-Fernández
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Datasets Mentioned

BETA
PRJNA518140

Methods Mentioned

BETA
flow cytometry
ELISA
PCR
nuclear magnetic resonance
transgenic
FCS
scraping
FACS
16S
NMR

Software Mentioned

Zen
QIIME
ImageJ
MATLAB
R
UCLUST
house
FastTree2

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