Protein Palmitoylation by ZDHHC13 Protects Skin against Microbial-Driven Dermatitis

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

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)894-904
Number of pages11
JournalJournal of Investigative Dermatology
Volume137
Issue number4
DOIs
StatePublished - Apr 1 2017
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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  • Cite this

    Chen, L. Y., Yang-Yen, H. F., Tsai, C. C., Thio, C. L. P., Chuang, H. L., Yang, L. T., Shen, L. F., Song, I. W., Liu, K. M., Huang, Y. T., Liu, F-T., Chang, Y. J., Chen, Y. T., & Yen, J. J. Y. (2017). Protein Palmitoylation by ZDHHC13 Protects Skin against Microbial-Driven Dermatitis. Journal of Investigative Dermatology, 137(4), 894-904. https://doi.org/10.1016/j.jid.2016.12.011