026 Targeting pathogenic MICA-NKG2D interactions by statins: A novel adjunct treatment strategy for alopecia areata management?

JAK inhibitors (JAKi), a major advance in AA therapy may not restore hair follicle’s (HF) physiological immune privilege (IP). Yet, HF IP collapse is required for to develop, while HFs with intact/restored are relatively AA-resistant. Therefore, additional therapeutics needed that target pathogenic pathways unaffected by JAKi. Namely, NKG2D on T and NK cells activated the epithelial distress signal, MICA (e.g., “stressed” HFs), leading collapse-inducing IFNg secretion T/NK cells. Statins up-regulate expression/activity of metalloproteinases, ADAM10 17, which enhance shedding suppress MICA-NKG2D interactions. To test this hypothesis an context, we have co-cultured human outer root sheath keratinocytes (ORS-KCs) Vd1+T Cells (TCs). These transitional immunity TCs increased both lesional non-lesional skin, secrete via above mechanism, attack AA-like manner ex vivo. ORS-KCs were pre-treated vehicle, or H2O2 imitate conditions oxidative damage-induced stress. After 24h, equal number dermal Vd1+TCs was added 48h, followed FACS analysis. This showed become (increased CD69+/NKG2D+ expression) cytotoxic proteins (perforin, granzyme B) when INFg H2O2-treated ORS-KC. Moreover, expression up-regulated after stress, can be counteracted lovastatin treatment vitro. Lovastatin also up-regulates 17 ORS-KCs, should shedding. pilot study supports systematically re-examine well-tolerated statins as potential adjunct therapeutic future management down-regulates pathogenic, “innate” NKG2D-MICA