Regulation of humoral and cellular gut immunity by lamina propria dendritic cells expressing Toll-like receptor 5

Nat Immunol. 2008 Jul;9(7):769-76. doi: 10.1038/ni.1622. Epub 2008 May 30.

Abstract

The intestinal cell types responsible for defense against pathogenic organisms remain incompletely characterized. Here we identify a subset of CD11c(hi)CD11b(hi) lamina propria dendritic cells (LPDCs) that expressed Toll-like receptor 5 (TLR5) in the small intestine. When stimulated by the TLR5 ligand flagellin, TLR5(+) LPDCs induced the differentiation of naive B cells into immunoglobulin A-producing plasma cells by a mechanism independent of gut-associated lymphoid tissue. In addition, by a mechanism dependent on TLR5 stimulation, these LPDCs promoted the differentiation of antigen-specific interleukin 17-producing T helper cells and type 1 T helper cells. Unlike spleen DCs, the LPDCs specifically produced retinoic acid, which, in a dose-dependent way, supported the generation and retention of immunoglobulin A-producing cells in the lamina propria and positively regulated the differentiation interleukin 17-producing T helper cells. Our findings demonstrate unique properties of LPDCs and the importance of TLR5 for adaptive immunity in the intestine.

Publication types

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

MeSH terms

  • Animals
  • Antibody Formation*
  • B-Lymphocytes / immunology
  • Cells, Cultured
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Flagellin / immunology
  • Flow Cytometry
  • Immunity, Cellular*
  • Immunity, Mucosal*
  • Immunoglobulin A / biosynthesis
  • Immunoglobulin A / immunology
  • Immunohistochemistry
  • Lymphocyte Activation / immunology
  • Mice
  • Mucous Membrane / cytology
  • Mucous Membrane / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / immunology
  • Toll-Like Receptor 5 / biosynthesis*
  • Tretinoin / immunology
  • Tretinoin / metabolism

Substances

  • Immunoglobulin A
  • Toll-Like Receptor 5
  • Flagellin
  • Tretinoin