Regulation of T cell polarization using HIF1a stabilizer, Roxadustat in MC903 induced Atopic Dermatitis 2433

Abstract Description Atopic Dermatitis (AD) remains one of the most chronic inflammatory skin diseases and is strongly associated with other atopic diseases like asthma. Though Th2 response is known to be the main humoral response in AD, follicular helper T (Tfh) cells have been recently identified as key mediators in AD pathogenesis. AD presents with increased serum IgE levels and associated cytokines, IL4 and IL13. HIF1α, an oxygen dependent transcriptional activator involved in cellular metabolism, plays a major role in regulating immune cell effector functions. HIF1α stabilization prevents Tfh13 polarization and inhibits IgE+ B cell induction. We hypothesized that Roxadustat (FG-4592), a HIF-1α stabilizer would be associated with a decreased Tfh2 response. Auricles of C57BL/6 mice were treated with MC903 and house dust mite (HDM) for a period of 15 days. Ear thickness was measured throughout the model. Mice received topical treatment with Roxadustat after day six. Mice were euthanized on day 15; organs were harvested and processed for flow cytometry, sectioning and RNA isolation to determine AD associated gene expression. Topical treatment with Roxadustat inhibited AD in treated mice with a reduction in IgE+ and IgG1+ B cells. AD associated genes, MMP12, TSLP, GATA3 and CD14 were observed to be decreased in Roxadustat treated mice (n = 5/group p = <0.05). Overall, topical treatment of AD with HIF1a stabilizer, Roxadustat in mice is associated with a decrease in the progression of AD. Funding Sources Supported by funding from NIAID-NIH (R56AI139658) and NHLBI-NIH (R01HL162991) to RKM Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)