A novel autocrine-paracrine loop of TSLP in atopic dermatitis is modulated by p63. (71.4)

Abstract Atopic dermatitis (AD) is a common disease affecting over 10% of children and adults, which severely impairs quality of life. Accumulating evidence has revealed that thymic stromal lymphopoietin (TSLP) of a pleiotropic cytokine play a critical role in the maintenance of AD. Currently, epidermal cells of AD are postulated as a major producer of TSLP, eventually leading to unfavorable local inflammation. However a property of the epidermal cells of AD is largely unknown. In the present study we assessed a functional significance of an epitheliotropic transcription factor p63 of a p53 homologue in the skin lesions of AD. Interestingly immunohistochemical analysis indicated constitutive downregulation of p63 of the epidermal cells in AD-affected skin areas. Further in vitro experiments using primary epidermal cells demonstrated that TSLP stimulation efficiently allowed cells to secrete TSLP as well as several inflammatory cytokines. Moreover it was found that the levels of expression of TSLP receptor (TSLPR) were under the control of p63. Collectively these indicate that the downregulation of p63 may cause chronic inflammation through providing a harmful TSLP-TSLPR axis to epidermal cells. Together with the evidence that innate ligands to TLRs like TLR3 could steadily suppress p63, our data would provide new insight into the pathogenesis of AD, especially with respect to the operation of innate immune responses by epidermal p63.