IRF4 Transcription-Factor-Dependent CD103(+)CD11b(+) Dendritic Cells Drive Mucosal T Helper 17 Cell Differentiation

Immunity. 2013 May 23;38(5):958-69. doi: 10.1016/j.immuni.2013.03.009. Epub 2013 May 9.

Abstract

CD103(+)CD11b(+) dendritic cells (DCs) represent the major migratory DC population within the small intestinal lamina propria (SI-LP), but their in vivo function remains unclear. Here we demonstrate that intestinal CD103(+)CD11b(+) DC survival was dependent on interferon regulatory factor 4 (IRF4). Mice with a DC deletion in Irf4 displayed reduced numbers of intestinal interleukin 17 (IL-17)-secreting helper T 17 (Th17) cells and failed to support Th17 cell differentiation in draining mesenteric lymph nodes (MLN) following immunization. The latter was associated with a selective reduction in CD103(+)CD11b(+) MLN DCs and DC derived IL-6. Immunized Il6(-/-) mice failed to support Th17 cell differentiation in MLN in vivo and CD103(+)CD11b(+) MLN DCs supported IL-6-dependent Th17 cell differentiation in vitro. Together, our results suggest a central role for IRF4-dependent, IL-6 producing CD103(+)CD11b(+) DCs in intestinal Th17 cell differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • CD11b Antigen / metabolism
  • Cell Differentiation
  • Cell Survival
  • Cells, Cultured
  • Dendritic Cells / metabolism*
  • Humans
  • Integrin alpha Chains / metabolism
  • Interferon Regulatory Factors / genetics
  • Interferon Regulatory Factors / metabolism*
  • Interleukin-17 / metabolism*
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / immunology
  • Lymph Nodes / cytology
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Sequence Deletion
  • Th17 Cells / immunology*
  • Th17 Cells / physiology*

Substances

  • Antigens, CD
  • CD11b Antigen
  • Integrin alpha Chains
  • Interferon Regulatory Factors
  • Interleukin-17
  • alpha E integrins
  • interferon regulatory factor-4