US EPA

3502713 

Journal Article 

Th2 responses are primed by skin dendritic cells with distinct transcriptional profiles 

Connor, LM; Tang, SC; Cognard, E; Ochiai, S; Hilligan, KL; Old, SI; Pellefigues, C; White, RF; Patel, D; Smith, AA; Eccles, DA; Lamiable, O; Mcconnell, MJ; Ronchese, F 

2017 

Yes 

Journal of Experimental Medicine
ISSN: 0022-1007
EISSN: 1540-9538 

214 

1 

125-142 

English 

27913566 

10.1084/jem.20160470 

WOS:000391123600011 

https://search.proquest.com/docview/1983435606?accountid=171501
Exit
 

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. 

Medical Sciences--Experimental Medicine, Laboratory Technique; Leukocyte migration; Stimuli; Immune response; Gene sequencing; Migration; Thymic stromal lymphopoietin; Lymphocytes T; Transcription; Dendritic cells; Animal models; Dibutyl phthalate; Interferon; Priming; Interleukin 4; Lymphocytes; Ribonucleic acid--RNA; Muridae