Bile retinoids imprint intestinal CD103+ dendritic cells with the ability to generate gut-tropic T cells

Mucosal Immunol. 2011 Jul;4(4):438-47. doi: 10.1038/mi.2010.91. Epub 2011 Feb 2.


Small intestinal lamina propria (SI-LP) CD103(+) dendritic cells (DCs) are imprinted with an ability to metabolize vitamin A (retinol), a property underlying their enhanced capacity to induce the gut-homing receptors CC chemokine receptor-9 and α4β7 on responding T cells. In this study, we demonstrate that imprinting of CD103(+) DCs is itself critically dependent on vitamin A and occurs locally within the small intestine (SI). The major vitamin A metabolite retinoic acid (RA) induced retinol-metabolizing activity in DCs both in vitro and in vivo, suggesting a direct role for RA in this process. Consistent with this, SI-LP CD103(+) DCs constitutively received RA signals in vivo at significantly higher levels than did colonic CD103(+) DCs. Remarkably, SI CD103(+) DCs remained imprinted in mice depleted of dietary but not of systemic retinol. We found that bile contained high levels of retinol, induced RA receptor-dependent retinol-metabolizing activity in bone marrow-derived DCs, and imprinted these cells with the ability to generate gut-tropic T cells. Taken together, these results suggest a novel and unexpected role for bile in SI-LP CD103(+) DC imprinting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / immunology
  • Antigens, CD / metabolism
  • Bile / chemistry
  • Bile / immunology
  • Bile / metabolism*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism*
  • Diet
  • Integrin alpha Chains / immunology
  • Integrin alpha Chains / metabolism
  • Intestinal Mucosa / metabolism*
  • Intestines / immunology*
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Receptors, CCR / metabolism
  • Retinoids / immunology
  • Retinoids / metabolism*
  • Signal Transduction / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • Vitamin A / analysis


  • Antigens, CD
  • CC chemokine receptor 9
  • Integrin alpha Chains
  • Receptors, CCR
  • Retinoids
  • alpha E integrins
  • Vitamin A