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

Sen Wang, Eduardo J. Villablanca, Jaime De Calisto, Daniel C.O. Gomes, Deanna D. Nguyen, Emiko Mizoguchi, Jonathan C. Kagan, Hans Christian Reinecker, Nir Hacohen, Cathryn Nagler, Ramnik J. Xavier, Bartira Rossi-Bergmann, Yi Bin Chen, Rune Blomhoff, Scott B. Snapper, J. Rodrigo Mora

Research output: Contribution to journalArticle

59 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)141-150
Number of pages10
JournalJournal of Immunology
Volume187
Issue number1
DOIs
StatePublished - Jul 1 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Wang, S., Villablanca, E. J., De Calisto, J., Gomes, D. C. O., Nguyen, D. D., Mizoguchi, E., Kagan, J. C., Reinecker, H. C., Hacohen, N., Nagler, C., Xavier, R. J., Rossi-Bergmann, B., Chen, Y. B., Blomhoff, R., Snapper, S. B., & Mora, J. R. (2011). MyD88-dependent TLR1/2 signals educate dendritic cells with gut-specific imprinting properties. Journal of Immunology, 187(1), 141-150. https://doi.org/10.4049/jimmunol.1003740