Galectin 7 promotes skin carcinogenesis through induction of myeloid regulatory cells

NICOLAS PINTO; CERLIANI J. P.; GABRIEL A. RABINOVICH

Congreso; 15th international workshop on Langerhans cells; 2017

Skin immunity is finely regulated by a broad network of cytokines and growth factors presentin the epidermis and dermis to maintain tissue homeostasis. Disruption of this cellular andmolecular balance may trigger different skin inflammatory diseases including psoriasis anddermatitis or neoplastic transformations like squamous cell carcinoma. Galectins (Gals), afamily of beta-galactoside proteins that signal via glycosylated receptors, have emerged as keyregulators of immune cell homeostasis. Galectin-7 (Gal7) is abundant in keratinocytes and istightly regulated in response to skin environmental stress, suggesting that its alteredexpression may contribute to skin disease. The aim of this study was to evaluate the role ofGal7 during skin carcinogenesis. Using bioinformatic analysis (AGREGAR CUAL) we found thatseveral oncogenic drivers (SOX2, NRAS, FOS, CD44 and RAC1 among others) were up-regulatedin transgenic mice (Tg46) over-expressing Gal7 under the K14 promoter as, compared to wildtype (WT) and Gal7-deficient (Lgals7 -/- ) mice. This expression profile positively correlated with ahigher number of skin papillomas developed in the skin of Tg46 mice compared to WT orLgals7 -/- animals. Notably, these mice were more susceptible to two-stage induced-carcinogenesis and developed papillomas at day 45, whereas WT and Lgals7 -/- animalsdeveloped skin lesions at day 53 and 60 respectively. Interestingly, Tg46 mice overexpressingGal7 in keratinocytes exhibited a higher percentage of myeloid-derived suppressor cells(MDSCs) in the spleen compared to their WT counterpart. MDSCs purified from Tg46 miceshowed enhanced immunosuppressive activity as compared to WT and Lgals7 -/- MDSCs in invitro lymphoproliferation assay. This enhanced immunosuppressive effect may account forincreased tumor susceptibility in vivo. In conclusion, altered expression of Gal7 may contributeto skin carcinogenesis by favoring dysregulation of oncogenic drivers and promoting expansionof immunosuppressive MDSCs.