Intestinal CD103(-) dendritic cells migrate in lymph and prime effector T cells

Mucosal Immunol. 2013 Jan;6(1):104-13. doi: 10.1038/mi.2012.53. Epub 2012 Jun 20.

Abstract

Intestinal dendritic cells (DCs) continuously migrate through lymphatics to mesenteric lymph nodes where they initiate immunity or tolerance. Recent research has focused on populations of intestinal DCs expressing CD103. Here we demonstrate, for the first time, the presence of two distinct CD103(-) DC subsets in intestinal lymph. Similar to CD103(+) DCs, these intestine-derived CD103(-) DCs are responsive to Flt3 and they efficiently prime and confer a gut-homing phenotype to naive T cells. However, uniquely among intestinal DCs, CD103(-) CD11b(+) CX(3)CR1(int) lymph DCs induce the differentiation of both interferon-γ and interleukin-17-producing effector T cells, even in the absence of overt stimulation. Priming by CD103(-) CD11b(+) DCs represents a novel mechanism for the rapid generation of effector T-cell responses in the gut. Therefore, these cells may prove to be valuable targets for the treatment of intestinal inflammation or in the development of effective oral vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehyde Dehydrogenase / metabolism
  • Animals
  • Antigens, CD / metabolism*
  • CD11b Antigen / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8 Antigens / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Movement / immunology*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism*
  • Immunophenotyping
  • Integrin alpha Chains / metabolism*
  • Interferon-gamma / biosynthesis
  • Interleukin-17 / biosynthesis
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / metabolism
  • Lymph / cytology
  • Lymph / immunology*
  • Lymphocyte Activation
  • Male
  • Membrane Proteins / metabolism
  • Mice
  • Receptors, CCR / metabolism
  • T-Lymphocyte Subsets / immunology*

Substances

  • Antigens, CD
  • CC chemokine receptor 9
  • CD11b Antigen
  • CD8 Antigens
  • CD8 antigen, alpha chain
  • Integrin alpha Chains
  • Interleukin-17
  • Membrane Proteins
  • Receptors, CCR
  • alpha E integrins
  • flt3 ligand protein
  • Interferon-gamma
  • Aldehyde Dehydrogenase