Keratinocytes control skin immune homeostasis through de novo–synthesized glucocorticoids
Truong San Phan, Leonhard Schink, Jasmin Mann, Verena M. Merk, Pascale Zwicky, Sarah Mundt, Dagmar Simon, Dagmar Kulms, Susanne Abraham, Daniel F. Legler, Mario Noti, Thomas Brunner
Abstract
ablation and long-term GC deficiency in keratinocytes primed the murine skin immune system resulting in spontaneous skin inflammation. Deficient skin GC in experimental models for inflammatory skin disorders led to exacerbated contact hypersensitivity and psoriasiform skin inflammation accompanied by decreased regulatory T cells and the involvement of unconventional T cells. Our findings provide insights on how skin homeostasis and pathology are critically regulated by keratinocyte-derived GC, emphasizing the immunoregulatory potential of endogenous GC in the regulation of epithelial immune microenvironment.