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Cell Death Dis. 2018 Dec 5;9(12):1181. doi: 10.1038/s41419-018-1226-1.

Elovl6 regulates mechanical damage-induced keratinocyte death and skin inflammation.

Author information

1
Department of Immunology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
2
Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
3
Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
4
International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
5
AMED-CREST, Japan Agency for Medical Research and Development (AMED), 1-7-1, Ohte-machi, Chiyoda-ku, Tokyo, 100-0004, Japan.
6
Department of Immunology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan. chigusano@md.tsukuba.ac.jp.
7
Department of Immunology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan. ashibuya@md.tsukuba.ac.jp.
8
Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan. ashibuya@md.tsukuba.ac.jp.

Abstract

Mechanical damage on the skin not only affects barrier function but also induces various immune responses, which trigger or exacerbate skin inflammation. However, how mechanical damage-induced skin inflammation is regulated remains incompletely understood. Here, we show that keratinocytes express the long-chain fatty-acid elongase Elovl6. Mice deficient in Elovl6 showed higher levels of cis-vaccenic acid (CVA) in the epidermis and severe skin inflammation induced by mechanical damage due to tape stripping than did wild-type mice. CVA accelerated tape stripping-triggered keratinocyte death and release of danger-associated molecular patterns (DAMPs) such as high-mobility group box 1 protein (HMGB-1) and IL-1α, which induced production of proinflammatory cytokines and chemokines IL-1β and CXCL-1 by keratinocytes. Our results demonstrate that Elovl6 regulates mechanical damage-triggered keratinocyte death and the subsequent dermatitis.

PMID:
30518914
PMCID:
PMC6281680
DOI:
10.1038/s41419-018-1226-1
[Indexed for MEDLINE]
Free PMC Article

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