title: Protein Palmitoylation by ZDHHC13 Protects Skin against Microbial-Driven Dermatitis.
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.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; Taiwan Mouse Clinic, Academia Sinica, Taipei, Taiwan.
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Chen
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
authors.forename: Hsin-Fang
authors.initials: HF
authors.lastname: Yang-Yen
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Chun-Chou
authors.initials: CC
authors.lastname: Tsai
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; Taiwan International Graduate Program (TIGP) in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan.
authors.forename: Christina Li-Ping
authors.initials: CL
authors.lastname: Thio
authors.affiliation: National Laboratory Animal Center, National Applied Research Laboratories, Taipei, Taiwan.
authors.forename: Hsiao-Li
authors.initials: HL
authors.lastname: Chuang
authors.affiliation: Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Miaoli, Taiwan.
authors.forename: Liang-Tung
authors.initials: LT
authors.lastname: Yang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Li-Fen
authors.initials: LF
authors.lastname: Shen
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: I-Wen
authors.initials: IW
authors.lastname: Song
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Kai-Ming
authors.initials: KM
authors.lastname: Liu
authors.affiliation: National Laboratory Animal Center, National Applied Research Laboratories, Taipei, Taiwan.
authors.forename: Yen-Te
authors.initials: YT
authors.lastname: Huang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Fu-Tong
authors.initials: FT
authors.lastname: Liu
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Ya-Jen
authors.initials: YJ
authors.lastname: Chang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Yuan-Tsong
authors.initials: YT
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; Taiwan Mouse Clinic, Academia Sinica, Taipei, Taiwan. Electronic address: bmjyen@ibms.sinica.edu.tw.
authors.forename: Jeffrey J Y
authors.initials: JJY
authors.lastname: Yen
mesh_terms: D000217:Acyltransferases / Q000235:genetics*; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001707:Biopsy, Needle; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D003872:Dermatitis / Q000382:microbiology* / Q000473:pathology; D003876:Dermatitis, Atopic / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D007150:Immunohistochemistry; D054878:Lipoylation / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D011897:Random Allocation; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D016207:Cytokines; D000217:Acyltransferases; C552301:Zdhhc13 protein, mouse