title: MyD88-dependent TLR1/2 signals educate dendritic cells with gut-specific imprinting properties.
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.
authors.affiliation: Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Sen
authors.initials: S
authors.lastname: Wang
authors.forename: Eduardo J
authors.initials: EJ
authors.lastname: Villablanca
authors.forename: Jaime
authors.initials: J
authors.lastname: De Calisto
authors.forename: Daniel C O
authors.initials: DC
authors.lastname: Gomes
authors.forename: Deanna D
authors.initials: DD
authors.lastname: Nguyen
authors.forename: Emiko
authors.initials: E
authors.lastname: Mizoguchi
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Kagan
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Reinecker
authors.forename: Nir
authors.initials: N
authors.lastname: Hacohen
authors.forename: Cathryn
authors.initials: C
authors.lastname: Nagler
authors.forename: Ramnik J
authors.initials: RJ
authors.lastname: Xavier
authors.forename: Bartira
authors.initials: B
authors.lastname: Rossi-Bergmann
authors.forename: Yi-Bin
authors.initials: YB
authors.lastname: Chen
authors.forename: Rune
authors.initials: R
authors.lastname: Blomhoff
authors.forename: Scott B
authors.initials: SB
authors.lastname: Snapper
authors.forename: J Rodrigo
authors.initials: JR
authors.lastname: Mora
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D018392:Genomic Imprinting / Q000276:immunology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011828:Radiation Chimera; D016201:Receptors, Lymphocyte Homing / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D051194:Toll-Like Receptor 1 / Q000502:physiology*; D051195:Toll-Like Receptor 2 / Q000502:physiology*
chemical_list: C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016201:Receptors, Lymphocyte Homing; C493486:Tlr2 protein, mouse; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2