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ZAG Regulates the Skin Barrier and Immunity in Atopic Dermatitis

 Ji Yeon Noh  ;  Jung U Shin  ;  Ji Hye Kim  ;  Seo Hyeong Kim  ;  Bo-Mi Kim  ;  Young Hwan Kim  ;  Semin Park  ;  Tae-Gyun Kim  ;  Kyong-Oh Shin  ;  Kyungho Park  ;  Kwang Hoon Lee 
 JOURNAL OF INVESTIGATIVE DERMATOLOGY, Vol.139(8) : 1648-1657.e7, 2019-08 
Journal Title
Issue Date
ADAM17 Protein / immunology ; ADAM17 Protein / metabolism ; Adipokines ; Administration, Topical ; Animals ; Biomarkers / analysis ; Biomarkers / metabolism ; Carrier Proteins / administration & dosage ; Carrier Proteins / genetics ; Carrier Proteins / immunology* ; Carrier Proteins / metabolism ; Cell Line ; Dermatitis, Atopic / diagnosis ; Dermatitis, Atopic / drug therapy ; Dermatitis, Atopic / immunology* ; Dermatitis, Atopic / pathology ; Disease Models, Animal ; Female ; Filaggrin Proteins ; Glycoproteins / administration & dosage ; Glycoproteins / genetics ; Glycoproteins / immunology* ; Glycoproteins / metabolism ; Humans ; Injections, Intradermal ; Keratinocytes ; Lipid Metabolism / genetics ; Lipid Metabolism / immunology ; Mice ; Permeability ; RNA, Small Interfering / metabolism ; Recombinant Proteins / administration & dosage ; Recombinant Proteins / immunology ; Recombinant Proteins / metabolism ; Skin / immunology ; Skin / metabolism ; Skin / pathology* ; T-Lymphocytes / immunology ; T-Lymphocytes / metabolism
Adipokines modulate immune responses and lipid metabolism in allergic disease; however, little is known about their role in the skin barrier and atopic dermatitis (AD). We identified ZAG, an adipokine that regulates lipid mobilization, as a biomarker for AD. ZAG levels were consistently decreased in sera, T cells, and skin in human AD patients compared with healthy controls. ZAG was primarily detected in the stratum corneum along with FLG and LOR. Knockdown of ZAG with short hairpin RNA resulted in decreased FLG and increased TSLP. Topical ZAG treatment in AD mice recovered ZAG expression in the skin and improved AD-like symptoms, transepidermal water loss, and ceramide levels. Furthermore, topical ZAG treatment induced immunoregulatory effects, including reduction of IL-4, IL-17, and IFN-gamma and increased Foxp3 in the skin and lymphoid organs. Interestingly, ZAG treatment also recovered decreased levels of ADAM17, an important player in skin barrier function and immune response in AD. Thus, ZAG deficiency is closely related to skin barrier function and the immune abnormalities of AD, and we suggest that restoration of ZAG may be a promising therapeutic option for the treatment of AD.
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Tae-Gyun(김태균) ORCID logo https://orcid.org/0000-0002-2116-4579
Noh, Ji Yeon(노지연)
Lee, Kwang Hoon(이광훈)
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