Protein Palmitoylation by ZDHHC13 Protects Skin against Microbial-Driven Dermatitis.

The Journal of investigative dermatology 2017 Apr

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Atopic dermatitis is a complex chronic inflammatory skin disorder that results from intimate interactions among genetic predisposition, host environment, skin barrier defects, and immunological factors. However, a clear genetic roadmap leading to atopic dermatitis remains to be fully explored. From a genome-wide mutagenesis screen, deficiency of ZDHHC13, a palmitoylacyl transferase, has previously been associated with skin and multitissue inflammatory phenotypes. Here, we report that ZDHHC13 is required for skin barrier integrity and that deficiency of ZDHHC13 renders mice susceptible to environmental bacteria, resulting in persistent skin inflammation and an atopic dermatitis-like disease. This phenotype is ameliorated in a germ-free environment and is also attenuated by antibiotic treatment, but not by deletion of the Rag1 gene, suggesting that a microbial factor triggers inflammation rather than intrinsic adaptive immunity. Furthermore, skin from ZDHHC13-deficient mice has both elevated levels of IL-33 and type 2 innate lymphoid cells, reinforcing the role of innate immunity in the development of atopic dermatitis. In summary, our study suggests that loss of ZDHHC13 in skin impairs the integrity of multiple barrier functions and leads to a dermatitis lesion in response to microbial encounters. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Li-Ying Chen, Hsin-Fang Yang-Yen, Chun-Chou Tsai, Christina Li-Ping Thio, Hsiao-Li Chuang, Liang-Tung Yang, Li-Fen Shen, I-Wen Song, Kai-Ming Liu, Yen-Te Huang, Fu-Tong Liu, Ya-Jen Chang, Yuan-Tsong Chen, Jeffrey J Y Yen. Protein Palmitoylation by ZDHHC13 Protects Skin against Microbial-Driven Dermatitis. The Journal of investigative dermatology. 2017 Apr;137(4):894-904