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

5 Citations (Scopus)

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

Fingerprint

Dermatitis
Lipoylation
Skin
Atopic Dermatitis
Proteins
Genes
Inflammation
Phenotype
Mutagenesis
Gene Deletion
Immunologic Factors
Adaptive Immunity
Genetic Predisposition to Disease
Transferases
Innate Immunity
Interleukin-2
Bacteria
Genome
Lymphocytes
Anti-Bacterial Agents

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Chen, L. Y., Yang-Yen, H. F., Tsai, C. C., Thio, C. L. P., Chuang, H. L., Yang, L. 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

Protein Palmitoylation by ZDHHC13 Protects Skin against Microbial-Driven Dermatitis. / Chen, Li Ying; Yang-Yen, Hsin Fang; Tsai, Chun Chou; Thio, Christina Li Ping; Chuang, Hsiao Li; Yang, Liang Tung; Shen, Li Fen; Song, I. Wen; Liu, Kai Ming; Huang, Yen Te; Liu, Fu-Tong; Chang, Ya Jen; Chen, Yuan Tsong; Yen, Jeffrey J.Y.

In: Journal of Investigative Dermatology, Vol. 137, No. 4, 01.04.2017, p. 894-904.

Research output: Contribution to journalArticle

Chen, LY, Yang-Yen, HF, Tsai, CC, Thio, CLP, Chuang, HL, Yang, LT, Shen, LF, Song, IW, Liu, KM, Huang, YT, Liu, F-T, Chang, YJ, Chen, YT & Yen, JJY 2017, 'Protein Palmitoylation by ZDHHC13 Protects Skin against Microbial-Driven Dermatitis', Journal of Investigative Dermatology, vol. 137, no. 4, pp. 894-904. https://doi.org/10.1016/j.jid.2016.12.011
Chen, Li Ying ; Yang-Yen, Hsin Fang ; Tsai, Chun Chou ; Thio, Christina Li Ping ; Chuang, Hsiao Li ; Yang, Liang Tung ; Shen, Li Fen ; Song, I. Wen ; Liu, Kai Ming ; Huang, Yen Te ; Liu, Fu-Tong ; Chang, Ya Jen ; Chen, Yuan Tsong ; Yen, Jeffrey J.Y. / Protein Palmitoylation by ZDHHC13 Protects Skin against Microbial-Driven Dermatitis. In: Journal of Investigative Dermatology. 2017 ; Vol. 137, No. 4. pp. 894-904.
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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.",
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