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

Research output: Contribution to journalArticlepeer-review

Authors

  • Felipe Melo-Gonzalez
  • Hana Kammoun
  • Elza Evren
  • Emma E Dutton
  • Markella Papadopoulou
  • Barry M Bradford
  • Ceylan Tanes
  • Fahmina Fardus-Reid
  • Jonathan R Swann
  • Kyle Bittinger
  • Neil A Mabbott
  • Bruce A Vallance
  • Tim Willinger
  • Matthew R Hepworth

Colleges, School and Institutes

External organisations

  • Manchester Collaborative Centre for Inflammation Research, Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
  • Karolinska Institutet
  • University of Manchester
  • University of Edinburgh
  • Children's Hospital of Philadelphia
  • Imperial College London
  • University of British Columbia

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 generation of T cell-dependent colonic IgA and suggest ILC3 act to maintain tissue homeostasis and mutualism with the mucosal-dwelling commensal microbiota.

Bibliographic note

© 2019 Melo-Gonzalez et al.

Details

Original languageEnglish
Pages (from-to)728-742
Number of pages15
JournalThe Journal of Experimental Medicine
Volume216
Issue number4
Early online date27 Feb 2019
Publication statusPublished - 1 Apr 2019

ASJC Scopus subject areas