MyD88-dependent TLR1/2 signals educate dendritic cells with gut-specific imprinting properties

J Immunol. 2011 Jul 1;187(1):141-50. doi: 10.4049/jimmunol.1003740. Epub 2011 Jun 6.

Abstract

Gut-associated dendritic cells (DC) synthesize all-trans retinoic acid, which is required for inducing gut-tropic lymphocytes. Gut-associated DC from MyD88(-/-) mice, which lack most TLR signals, expressed low levels of retinal dehydrogenases (critical enzymes for all-trans retinoic acid biosynthesis) and were significantly impaired in their ability to induce gut-homing T cells. Pretreatment of extraintestinal DC with a TLR1/2 agonist was sufficient to induce retinal dehydrogenases and to confer these DC with the capacity to induce gut-homing lymphocytes via a mechanism dependent on MyD88 and JNK/MAPK. Moreover, gut-associated DC from TLR2(-/-) mice, or from mice in which JNK was pharmacologically blocked, were impaired in their education to imprint gut-homing T cells, which correlated with a decreased induction of gut-tropic T cells in TLR2(-/-) mice upon immunization. Thus, MyD88-dependent TLR2 signals are necessary and sufficient to educate DC with gut-specific imprinting properties and contribute in vivo to the generation of gut-tropic T cells.

Publication types

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

MeSH terms

  • Animals
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / metabolism
  • Cell Line, Tumor
  • Coculture Techniques
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism*
  • Genomic Imprinting / immunology*
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / metabolism
  • Melanoma, Experimental
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Myeloid Differentiation Factor 88 / deficiency
  • Myeloid Differentiation Factor 88 / genetics
  • Myeloid Differentiation Factor 88 / physiology*
  • Radiation Chimera
  • Receptors, Lymphocyte Homing / deficiency
  • Receptors, Lymphocyte Homing / genetics
  • Receptors, Lymphocyte Homing / physiology
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • Toll-Like Receptor 1 / physiology*
  • Toll-Like Receptor 2 / physiology*

Substances

  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Receptors, Lymphocyte Homing
  • Tlr2 protein, mouse
  • Toll-Like Receptor 1
  • Toll-Like Receptor 2