TY - JOUR
T1 - MyD88-dependent TLR1/2 signals educate dendritic cells with gut-specific imprinting properties
AU - Wang, Sen
AU - Villablanca, Eduardo J.
AU - De Calisto, Jaime
AU - Gomes, Daniel C.O.
AU - Nguyen, Deanna D.
AU - Mizoguchi, Emiko
AU - Kagan, Jonathan C.
AU - Reinecker, Hans Christian
AU - Hacohen, Nir
AU - Nagler, Cathryn
AU - Xavier, Ramnik J.
AU - Rossi-Bergmann, Bartira
AU - Chen, Yi Bin
AU - Blomhoff, Rune
AU - Snapper, Scott B.
AU - Mora, J. Rodrigo
PY - 2011/7/1
Y1 - 2011/7/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.1003740
DO - 10.4049/jimmunol.1003740
M3 - Article
C2 - 21646294
AN - SCOPUS:79960400021
SN - 0022-1767
VL - 187
SP - 141
EP - 150
JO - Journal of Immunology
JF - Journal of Immunology
IS - 1
ER -