GALECTIN 7 PROMOTES CHEMICAL SKIN CAR- CINOGENESIS THROUGH INDUCTION OF MYELOID REGULATORY CELLS IN MICE

PINTO NA; MORALES R; GATTO S; BLINDER A; CROCI D; ABBA MC; RABINOVICH G; CERLIANI J

Buenos Aires

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

Skin immunity is finely regulated by a broad network of cytokinesand growth factors present in the epidermis and dermis to maintaintissue homeostasis. Disruption of this cellular and molecular balancemay trigger different skin inflammatory diseases including psoriasisand dermatitis or neoplastic transformations like squamous cell car-cinoma. Galectins (Gals), a family of beta-galactoside proteins thatsignal via glycosylated receptors, have emerged as key regulatorsof immune cell homeostasis. Galectin-7 (Gal7) is abundant in kera-tinocytes and is tightly regulated in response to skin environmentalstress, suggesting that its altered expression may contribute to skindisease. The aim of this study was to evaluate the role of Gal7 duringskin carcinogenesis. Using bioinformatic analysis (Enrichr resourceand Cytoscape ́s plugins ClueGo/CluePedia) we found that sever-al oncogenic drivers (SOX2, NRAS, FOS, CD44 and RAC1 amongothers) were up-regulated in transgenic mice (Tg46) over-express-ing Gal7 under the K14 promoter as, compared to wild type (WT)and Gal7-deficient (Lgals7-/-) mice. This expression profile positive-ly correlated with a higher number of skin papillomas developed inthe skin of Tg46 mice compared to WT or Lgals7-/- animals. No-tably, these mice were more susceptible to two-stage induced-car-cinogenesis and developed papillomas at day 45, whereas WT andLgals7-/- animals developed skin lesions at day 53 and 60 respec-tively. Interestingly, Tg46 mice overexpressing Gal7 in keratinocytesexhibited a higher percentage of CD11b+Ly6G-Ly6C+ myeloid-de-rived suppressor cells (MDSCs,) in the spleen compared to theirWT counterpart. MDSCs purified from Tg46 mice showed enhancedimmunosuppressive activity as compared to WT and Lgals7-/- MD-SCs in in vitro lymphoproliferation assay. This enhanced immuno-suppressive effect may account for increased tumor susceptibilityin vivo. In conclusion, altered expression of Gal7 may contribute toskin carcinogenesis by favoring dysregulation of oncogenic driversand promoting expansion of immunosuppressive MDSCs.