國家衛生研究院 NHRI:Item 3990099045/10168
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    题名: Protein palmitoylation by ZDHHC13 protects skin against microbial-driven dermatitis
    作者: Chen, LY;Yang-Yen, HF;Tsai, CC;Thio, CL;Chuang, HL;Yang, LT;Shen, LF;Song, IW;Liu, KM;Huang, YT;Liu, FT;Chang, YJ;Chen, YT;Yen, JJ
    贡献者: Institute of Cellular and Systems Medicine
    摘要: Atopic dermatitis (AD) is a complex chronic inflammatory skin disorder that results from intimate interactions between genetic predisposition, host environment, skin barrier defects, and immunological factors. However, a clear genetic roadmap leading to AD remains to be fully explored. From a genome-wide mutagenesis screen, deficiency of ZDHHC13, a palmitoylacyl transferase, has previously been associated with skin and multi-tissue 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 AD-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 (ILC2s), reinforcing the role of innate immunity in the development of AD. 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.
    日期: 2017-04
    關聯: Journal of Investigative Dermatology. 2017 Apr;137(4):894-904.
    Link to: http://dx.doi.org/10.1016/j.jid.2016.12.011
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-202X&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000396884400018
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85015946198
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