489 Sphingosine 1-phosphate receptors are expressed in human scalp hair follicles and their modulation by etrasimod warrants further investigation for management of alopecia areata

Etrasimod is a selective sphingosine 1-phosphate receptor 1, 4, 5 (S1P1,4,5) modulator in development for alopecia areata (AA). S1P1 cell surface that regulates T trafficking from lymphoid organs to the periphery. In skin, S1P pathway has been shown be involved epidermal keratinocyte proliferation and differentiation. Hair follicles (HFs) also harbor keratinocytes are target of autoimmune responses AA. AA, HFs lose their immune privilege (IP), attacked by cells, prematurely enter catagen. this study, we evaluated expression S1P1,5 human investigated whether etrasimod beneficially impacts HF physiology pathology. By RNAseq, situ hybridization (ISH), immunostaining (IS), confirmed epithelium mesenchyme healthy scalp skin. Interestingly, intrafollicular epithelial these receptors was increased patients suffering AA had more perifollicular CD8+ cells expressing S1P1. To evaluate effects, were microdissected, treated ex vivo, analyzed IS RNAseq. treatment resulted tendentially remaining anagen preservation IP, revealed no change MHC class I expression. RNAseq data significant up-regulation genes hair keratinization. mimic AA-like inflammation, skin vivo with 100IU/ml IFNg IS. prevented IFNg-mediated inhibited increase CD8+, CD8+S1P1+, CD8-S1P1+ showing lymphocytic morphology. Taken together, initial results suggest novel role Further investigation as new oral therapeutic option warranted.