005 IL-9 promotes a pathogenic phenotype and enhances proliferation in skin-tropic TH cells

IL-9 is a pleiotropic cytokine, for which an overarching role in humans remains elusive. Recent research shows that Interleukin 9 (IL-9) and its receptor, IL-9R, are predominantly expressed by skin-tropic T helper 2 (TH2) cells. This hence suggests autocrine or paracrine signals play important cutaneous immunity allergy. Yet, the mechanism of action incompletely understood. Here, we aimed at deciphering effect on TH cells allergic skin inflammation. To this end, isolated human from acute atopic contact dermatitis biopsies, expressing high levels IL-9R. Transcriptional profiling showed approx. 800 genes differentially response to IL-9. Pathway analysis revealed upregulated associated with conventional TH2 immune response. Strikingly, observed strong induction specifically pathogenic phenotype, such as IL9, IL17RB HPGDS. In addition, found IL-9-stimulated coordinated involved aerobic glycolysis. On protein level, confirmed prominently induced expression monocarboxylate transporter 1 (MCT1), key export lactate, end product As functional consequence, boosted glycolytic capacity cell proliferation, was abrogated inhibition MCT1. Together, our data delineates not only promotes features, but also provides proliferative advantage These unrecognized roles might open up novel strategies targeted manipulation