Intestinal lamina propria dendritic cells maintain T cell homeostasis but do not affect commensalism

J Exp Med. 2013 Sep 23;210(10):2011-24. doi: 10.1084/jem.20130728. Epub 2013 Sep 9.

Abstract

Dendritic cells (DCs) in the intestinal lamina propria (LP) are composed of two CD103(+) subsets that differ in CD11b expression. We report here that Langerin is expressed by human LP DCs and that transgenic human langerin drives expression in CD103(+)CD11b(+) LP DCs in mice. This subset was ablated in huLangerin-DTA mice, resulting in reduced LP Th17 cells without affecting Th1 or T reg cells. Notably, cognate DC-T cell interactions were not required for Th17 development, as this response was intact in huLangerin-Cre I-Aβ(fl/fl) mice. In contrast, responses to intestinal infection or flagellin administration were unaffected by the absence of CD103(+)CD11b(+) DCs. huLangerin-DTA x BatF3(-/-) mice lacked both CD103(+) LP DC subsets, resulting in defective gut homing and fewer LP T reg cells. Despite these defects in LP DCs and resident T cells, we did not observe alterations of intestinal microbial communities. Thus, CD103(+) LP DC subsets control T cell homeostasis through both nonredundant and overlapping mechanisms.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • CD11b Antigen / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Diphtheria Toxin / genetics
  • Homeostasis / genetics
  • Homeostasis / immunology*
  • Humans
  • Immunophenotyping
  • Integrin alpha Chains / metabolism
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / microbiology*
  • Lectins, C-Type / genetics
  • Mannose-Binding Lectins / genetics
  • Metagenome
  • Mice
  • Mice, Transgenic
  • Phenotype
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Th17 Cells / immunology
  • Th17 Cells / metabolism

Substances

  • Antigens, CD
  • CD11b Antigen
  • CD207 protein, human
  • Diphtheria Toxin
  • Integrin alpha Chains
  • Lectins, C-Type
  • Mannose-Binding Lectins
  • alpha E integrins