ΔNp63 regulates IL-33 and IL-31 signaling in atopic dermatitis

Rizzo JM et al.

Cell Death Differ. 2016 Jan 15. doi: 10.1038/cdd.2015.162. [Epub ahead of print]

Speaker: Yi Sheng Jiang (江翊生)                                Time: 15:10~16:00, Apr. 27, 2016

Commentator: Dr. Jiu-Yao Wang (王志堯老師)          Place: Room 601

Abstract:

Atopic dermatitis (AD) is a chronic inflammatory skin disease, which is characterized by epidermal hyperplasia, aberrant keratinocyte differentiation, and elevated expression of cytokines and chemokines, which are present in AD. Growing evidence supports a role for p63 in a variety of epithelial diseases¹. ΔNp63 is one of the p63 isoform, which is highly expressed in keratinocytes and is indispensable for skin development². In this study, the authors show that ΔNp63 is expressed at elevated levels in human AD lesional skin. Furthermore, overexpression of ΔNp63 in the epidermis of transgenic mice results in a skin phenotype that shares many of the key features associated with human AD lesion, including pruritus, epidermal hyperplasia, altered terminal differenitation, and a inflammatory microenvironment. Besides, restoration of normal physiological levels of ΔNp63 in the mouse epidermis is sufficient to reverse the AD-like skn phenotype. The results also indicate that IL-33 and IL-31, key players of the skin lesions observed in AD, are direct transcirptional targets of ΔNp63 in keratinocytes³. Collectively, this study provides the potential role of ΔNp63-driven keratinocyte activation as a critical precursor in AD development.

References:

1.     Bieber T. Atopic dermatitis. N. Engl. J. Med. 2008: 358, 1483-1494.

2.     Romano RA, Amalley K, Magraw C, Serna VA, Kurita T, Raghavan S et al. ΔNp63 knockout mice reveal its indispensable role as a master regulator of epithelial development and differentiation. Development 2012; 139, 772-782.

3.     Imai Y, Yasuda K, Sakaguchi Y, Haneda T, Mizutani H, Yoshimoto T et al. Skin-specific expression of IL-33 activates group 2 innate lymphoid cells and elicits atopic dermatitis-like inflammation in mice. Proc, Natl, Acad, Sci, USA. 2013; 110: 13921-13926