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

• Published in: The Journal of immunology (1950) Vol. 187; no. 1; pp. 141 - 150
• Main Authors: Wang, Sen, Villablanca, Eduardo J, De Calisto, Jaime, Gomes, Daniel C O, Nguyen, Deanna D, Mizoguchi, Emiko, Kagan, Jonathan C, Reinecker, Hans-Christian, Hacohen, Nir, Nagler, Cathryn, Xavier, Ramnik J, Rossi-Bergmann, Bartira, Chen, Yi-Bin, Blomhoff, Rune, Snapper, Scott B, Mora, J Rodrigo
• Format: Journal Article
• Language: English
• Published: United States 01.07.2011
• Subjects: 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
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1003740

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.