CCR6 promotes steady-state mononuclear phagocyte association with the intestinal epithelium, imprinting and immune surveillance

Keely G. McDonald, Leroy W. Wheeler, Jeremiah R. McDole, Shannon Joerger, Jenny K. Gustafsson, Devesha H. Kulkarni, Kathryn A. Knoop, Ifor R. Williams, Mark J. Miller, Rodney D. Newberry

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

The intestinal lamina propria (LP) contains antigen-presenting cells with features of dendritic cells and macrophages, collectively referred to as mononuclear phagocytes (MNPs). Association of MNPs with the epithelium is thought to play an important role in multiple facets of intestinal immunity including imprinting MNPs with the ability to induce IgA production, inducing the expression of gut homing molecules on T cells, facilitating the capture of luminal antigens and microbes, and subsequent immune responses in the mesenteric lymph node (MLN). However, the factors promoting this process in the steady state are largely unknown, and in vivo models to test and confirm the importance of LP-MNP association with the epithelium for these outcomes are unexplored. Evaluation of epithelial expression of chemoattractants in mice where MNP–epithelial associations were impaired suggested CCL20 as a candidate promoting epithelial association. Expression of CCR6, the only known receptor for CCL20, was required for MNPs to associate with the epithelium. LP-MNPs from CCR6−/− mice did not display defects in acquiring antigen and stimulating T-cell responses in ex vivo assays or in responses to antigen administered systemically. However, LP-MNPs from CCR6-deficient mice were impaired at acquiring luminal and epithelial antigens, inducing IgA production in B cells, inducing immune responses in the MLN, and capturing and trafficking luminal commensal bacteria to the MLN. These findings identify a crucial role for CCR6 in promoting LP-MNPs to associate with the intestinal epithelium in the steady state to perform multiple functions promoting gut immune homeostasis.

Original languageEnglish
Pages (from-to)613-627
Number of pages15
JournalImmunology
Volume152
Issue number4
DOIs
StatePublished - Dec 2017

Keywords

  • bacteria
  • dietary antigen
  • intestine
  • mononuclear phagocyte

Fingerprint Dive into the research topics of 'CCR6 promotes steady-state mononuclear phagocyte association with the intestinal epithelium, imprinting and immune surveillance'. Together they form a unique fingerprint.

  • Cite this