Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid

J Exp Med. 2007 Aug 6;204(8):1775-85. doi: 10.1084/jem.20070602. Epub 2007 Jul 9.

Abstract

To maintain immune homeostasis, the intestinal immune system has evolved redundant regulatory strategies. In this regard, the gut is home to a large number of regulatory T (T reg) cells, including the Foxp3(+) T reg cell. Therefore, we hypothesized that the gut environment preferentially supports extrathymic T reg cell development. We show that peripheral conversion of CD4(+) T cells to T reg cells occurs primarily in gut-associated lymphoid tissue (GALT) after oral exposure to antigen and in a lymphopenic environment. Dendritic cells (DCs) purified from the lamina propria (Lp; LpDCs) of the small intestine were found to promote a high level of T reg cell conversion relative to lymphoid organ-derived DCs. This enhanced conversion by LpDCs was dependent on TGF-beta and retinoic acid (RA), which is a vitamin A metabolite highly expressed in GALT. Together, these data demonstrate that the intestinal immune system has evolved a self-contained strategy to promote T reg cell neoconversion.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Administration, Oral
  • Animals
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Proliferation
  • Dendritic Cells / cytology
  • Forkhead Transcription Factors / metabolism*
  • Forkhead Transcription Factors / physiology*
  • Immune System
  • Intestine, Small / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mucous Membrane / metabolism*
  • Spleen / metabolism
  • T-Lymphocytes, Regulatory / metabolism*
  • Tretinoin / metabolism*

Substances

  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Tretinoin