The intestinal micro-environment imprints stromal cells to promote efficient Treg induction in gut-draining lymph nodes

Mucosal Immunol. 2014 Mar;7(2):359-68. doi: 10.1038/mi.2013.54. Epub 2013 Aug 14.


De novo induction of Foxp3⁺ regulatory T cells (Tregs) is particularly efficient in gut-draining mesenteric and celiac lymph nodes (mLN and celLN). Here we used LN transplantations to dissect the contribution of stromal cells and environmental factors to the high Treg-inducing capacity of these LN. After transplantation into the popliteal fossa, mLN and celLN retained their high Treg-inducing capacity, whereas transplantation of skin-draining LN into the gut mesenteries did not enable efficient Treg induction. However, de novo Treg induction was abolished in the absence of dendritic cells (DC), indicating that this process depends on synergistic contributions of stromal and DC. Stromal cells themselves were influenced by environmental signals as mLN grafts taken from germ-free donors and celLN grafts taken from vitamin A-deficient donors did not show any superior Treg-inducing capacity. Collectively, our observations reveal a hitherto unrecognized role of LN stromal cells for the de novo induction of Foxp3⁺ Tregs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Communication
  • Cellular Microenvironment / immunology*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Forkhead Transcription Factors / metabolism
  • Immune Tolerance
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / microbiology
  • Intestines / cytology*
  • Intestines / immunology*
  • Intestines / microbiology
  • Lymph Nodes / immunology*
  • Mice
  • Mice, Knockout
  • Microbiota
  • Retinal Dehydrogenase / genetics
  • Retinal Dehydrogenase / metabolism
  • Stromal Cells / physiology*
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Vitamin A / metabolism


  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interleukin-6
  • Vitamin A
  • Retinal Dehydrogenase