102 IL-9 induces a type I interferon signature in pathogenic skin-tropic TH2 cells

IL-9 is a pleiotropic cytokine, for which an overarching role in humans remains elusive. Both interleukin 9 (IL-9) and its receptor, IL-9R, are specifically expressed by skin-tropic T helper 2 (TH2) cells. This suggests that signals play important cutaneous immunity allergy. Yet, the mechanism of action incompletely understood. In this study, we aimed at deciphering effect on TH cells allergic skin inflammation. We isolated human IL-9R+ TH2 from blood contact dermatitis performed transcriptional profiling presence IL-9. Our results show regulated expression approx. 800 genes. Upregulated genes were associated with immune response and, surprisingly, revealed strong induction interferon-stimulated (ISGs) such as IFIT3, RSAD2, OAS1. Moreover, enhanced i) IRF9 STAT1, together STAT2 form ISGF3 complex, ii) two subunits DTX3L-PARP9 dimer. Both, DTX3L-PARP9, well-known transcription factor complexes amplify type-1 interferon responses. Hence, our data induces type I signature sensitizes them to signals. Since ISG usually mediated through STAT1 phosphorylation, next investigated IL-9R signaling detail. Interestingly, found signal transduction indeed leads phosphorylation STAT3, STAT5 well STAT1. Thus, unique profile not comparable other members common gamma-chain-cytokine receptor family. summary, induce profile. Therefore, may enhance interferon-dependent type-2 inflammation thereby providing protection against viral infections.