335 HY209, a GPCR19 agonist, ameliorates atopic dermatitis in mice

Atopic dermatitis (AD) is a chronic inflammatory skin disorder which characterized by intense itch and eczematous lesions. Keratinocytes are pivotal cells in the pathogenesis of AD as much Th2 cells. Regulation pro-inflammatory features keratinocytes combination with T cell modulators such JAK inhibitors might hold promise for achieving disease control patients better than alone. In this regards, targeting NLRP3 inflammasome (N3I) skin-infiltrating/resident myeloid open new insight patient’s therapy. Due to presence polymorphisms, subtypes, ubiquitous expression, redundant pathways, inhibition N3I components ineffective disorders. We show that HY209 regulates both priming activation phases keratinocytes. receptor, GPCR19, colocalizes P2X7R enhance Ca++ mobilization leads activation. inhibits BzATP-mediated mobilization, suppresses expression addition inhibiting NF-kB via adenylate cyclase-PKA pathway Transcription components, oligomerization processing immature IL-1β IL-18 were suppressed treatment vitro vivo. Topical oral ameliorates mice induced DNCB further confirmation using MC903 oxazolone models. A keratinocytes-modulator like improve clinical symptoms synergistically when combined cell- modulators.