671 Impaired follicular Nrf2 signaling: Potential early therapeutic target in hidradenitis suppurativa

Hidradenitis suppurativa (HS) is a chronic debilitating disease characterized by inflammatory nodules and sinus tracts in areas rich terminal hair follicles apocrine glands. Lifestyle factors associated with oxidative stress, such as obesity smoking, worsen symptoms. An early step HS follicular dilation occlusion keratin, which results rupture robust response. Nrf2 signaling key regulator of response to environmental redox insults keratin expression. Herein, we utilized indirect immunofluorescence (IF) assess levels total phosphorylated (active) its inhibitor Keap1 lesional skin (n=10) sex-matched healthy controls (n=4). There was decrease IF signal for all three targets compared controls. Next, examined whether 16 (K16) may provide potential mechanistic link between dysfunctional hyperkeratinization follicles. K16 stress-inducible target signaling. Moreover, overexpression tissue-specific transgenic mouse model aberrant keratinization the outer root sheath. We found an upregulation both type II binding partner K6 hyperplastic sheath tracts. This suggest that impaired signaling, possibly virtue bidirectional regulatory relationship K16, contribute HS. Given growing evidence efficacy topical inducers attractiveness intervention HS, this work opens up new promising therapeutic avenues clinically devastating limited treatment options.