LB1002 Melanocyte depletion in vitiligo and canities is associated with M2 macrophage deficiency and responds to modulation by M2-secreted soluble mediator maresin 1 in vitro and in vivo

Melanocyte depletion occurs in vitiligo and aging associated hair greying (canities). Currently available therapies are unsatisfactory due to limited efficacy or therapy-related adverse effects. The purpose of our study is uncover previously unknown pathogenic pathways for canities develop that can block these pathways. Transcriptome sequencing-based immune cellular profiling was performed on skin biopsies from healthy volunteers (N=9) patients with (N=36) chronic dermatitis (N=15), revealing a 3-fold reduction M2 macrophages lesions (p=0.037). There no macrophage the dermatitis. In addition, serum levels maresin 1 (a soluble functional mediator macrophages) aged C57BL/J6 mice were significantly lower than age-and sex matched without (p=0.026). Further, addition culture medium increased survival melanocytes by more 50% (p<0.05). Intraperitoneal injection into inhibited development 43% (p<0.05) after TRP-2 immunization, abolished spontaneous aging-associated (canities) (p=0.0125). Taken together, results suggest deficiency shared mechanism melanocyte canities, agonists, such as other specialized pro-resolving molecules, may be effective prevention treatment conditions caused depletion, including canities.