title: Th2 responses are primed by skin dendritic cells with distinct transcriptional profiles.
abstract: The dendritic cell signals required for the in vivo priming of IL-4-producing T cells are unknown. We used RNA sequencing to characterize DCs from skin LN of mice exposed to two different Th2 stimuli: the helminth parasite Nippostrongylus brasiliensis (Nb) and the contact sensitizer dibutyl phthalate (DBP)-FITC. Both Nb and DBP-FITC induced extensive transcriptional changes that involved multiple DC subsets. Surprisingly, these transcriptional changes were highly distinct in the two models, with only a small number of genes being similarly regulated in both conditions. Pathway analysis of expressed genes identified no shared pathways between Nb and DBP-FITC, but revealed a type-I IFN (IFN-I) signature unique to DCs from Nb-primed mice. Blocking the IFN-I receptor at the time of Nb treatment had little effect on DC migration and antigen transport to the LN, but inhibited the up-regulation of IFN-I-induced markers on DCs and effectively blunted Th2 development. In contrast, the response to DBP-FITC was not affected by IFN-I receptor blockade, a finding consistent with the known dependence of this response on the innate cytokine TSLP. Thus, the priming of Th2 responses is associated with distinct transcriptional signatures in DCs in vivo, reflecting the diverse environments in which Th2 immune responses are initiated.
authors.affiliation: Malaghan Institute of Medical Research, Wellington 6012, New Zealand.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Connor
authors.affiliation: Malaghan Institute of Medical Research, Wellington 6012, New Zealand.
authors.forename: Shiau-Choot
authors.initials: SC
authors.lastname: Tang
authors.affiliation: Malaghan Institute of Medical Research, Wellington 6012, New Zealand.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Cognard
authors.affiliation: Malaghan Institute of Medical Research, Wellington 6012, New Zealand.|Department of Pathology and Molecular Medicine, University of Otago Wellington, Wellington 6242, New Zealand.
authors.forename: Sotaro
authors.initials: S
authors.lastname: Ochiai
authors.affiliation: Malaghan Institute of Medical Research, Wellington 6012, New Zealand.|Department of Pathology and Molecular Medicine, University of Otago Wellington, Wellington 6242, New Zealand.
authors.forename: Kerry L
authors.initials: KL
authors.lastname: Hilligan
authors.affiliation: Malaghan Institute of Medical Research, Wellington 6012, New Zealand.
authors.forename: Samuel I
authors.initials: SI
authors.lastname: Old
authors.affiliation: Malaghan Institute of Medical Research, Wellington 6012, New Zealand.
authors.forename: Christophe
authors.initials: C
authors.lastname: Pellefigues
authors.affiliation: Malaghan Institute of Medical Research, Wellington 6012, New Zealand.
authors.forename: Ruby F
authors.initials: RF
authors.lastname: White
authors.affiliation: Malaghan Institute of Medical Research, Wellington 6012, New Zealand.
authors.forename: Deepa
authors.initials: D
authors.lastname: Patel
authors.affiliation: Malaghan Institute of Medical Research, Wellington 6012, New Zealand.
authors.forename: Adam Alexander T
authors.initials: AA
authors.lastname: Smith
authors.affiliation: Malaghan Institute of Medical Research, Wellington 6012, New Zealand.
authors.forename: David A
authors.initials: DA
authors.lastname: Eccles
authors.affiliation: Malaghan Institute of Medical Research, Wellington 6012, New Zealand.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lamiable
authors.affiliation: School of Biological Sciences, Victoria University of Wellington, Wellington 6012, New Zealand.
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: McConnell
authors.affiliation: Malaghan Institute of Medical Research, Wellington 6012, New Zealand fronchese@malaghan.org.nz.|School of Biological Sciences, Victoria University of Wellington, Wellington 6012, New Zealand.
authors.forename: Franca
authors.initials: F
authors.lastname: Ronchese
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D007136:Immunoglobulins / Q000502:physiology; D007370:Interferon Type I / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009559:Nippostrongylus / Q000276:immunology; D053633:Receptor, Interferon alpha-beta / Q000502:physiology; D018121:Receptors, Cytokine / Q000502:physiology; D012867:Skin / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014158:Transcription, Genetic
chemical_list: C508032:Ifnar1 protein, mouse; D007136:Immunoglobulins; D007370:Interferon Type I; D018121:Receptors, Cytokine; C410591:Tslpr protein, mouse; D053633:Receptor, Interferon alpha-beta