Divergent Roles of Epithelium-Derived Alarmins in Notch Signaling-Deficient Skin

Abstract

Epithelium-derived alarmin cytokines, thymic stromal lymphopoietin (TSLP), Interleukin (IL)-33, and IL-25, polarize T cells toward the T H 2 phenotype at barrier sites to fight pathogens and allergens (Hammad and Lambrecht, 2015). T H 2 cells are increasingly recognized as key players in barrier repair to prevent tissue damage following environmental insults like parasite infection (Chen et al., 2012). Furthermore, TSLP-induced T H 2 cell immunity is critical for suppressing epithelial tumor development in mice (Demehri et al., 2016, Demehri et al., 2012 and humans (Cunningham et al., 2017). Therefore, the role that epithelium-derived alarmins play in controlling immune responses at barrier organs is of broad clinical relevance.Notch proteins function as tumor suppressors in the skin of mice and humans (Nicolas et al., 2003, Wang et al., 2011. Our previous investigations demonstrated that loss of epidermal Notch1 leads to a mild inflammatory infiltrate, activated dermal fibroblasts, expanded *