Role of JAK-1 dependent cytokines and the JAK/STAT pathway in skin barrier defects observed in Atopic Dermatitis
Atopic dermatitis (AD) is the most common chronic and relapsing inflammatory skin disease, affecting up to 15 million of Americans (about 17% of children and 6% adults). AD is typically characterized by impaired skin barrier function and skewed T helper (Th) 2 inflammation, yet other inflammatory profiles (Th1, Th17, Th22) have been observed in AD patients. How cytokines from these different Th subsets impact barrier function in this disease is currently being investigated. Janus kinase (JAK) inhibitors block cy-tokine-mediated signaling via the Janus kinase-signal transducer and activator of tran-scription (JAK-STAT) pathway, which plays an important role in immunoregulation and cell growth. JAK-STATs are heavily expressed in the epidermis and involved in critical epidermal barrier pathways.
A better understanding of the complex interactions between relevant AD-cytokines and how they affect epidermal barrier function is critical for a more thorough under-standing of AD pathogenesis and for the development of effective AD therapies. The purpose of the current application is to focus, in vitro, on the effect of JAK-1 dependent cytokines and the JAK/STAT downstream pathway on keratinocytes barrier structures, by investigating the effect of the selective JAK signaling pathways on keratinocytes terminal differentiation and Tight Junction (TJ) function.