title: Progranulin is preferentially expressed in patients with psoriasis vulgaris and protects mice from psoriasis-like skin inflammation.
abstract: Progranulin (PGRN) is a multi-functional protein known to be involved in inflammation. Recent studies have found that PGRN has dual roles in inflammation and exerts anti-inflammatory and pro-inflammatory function in different diseases. However, the role of PGRN in psoriasis has not been fully elucidated. Here, we detected preferential expression of PGRN in human psoriatic lesions and serum. Moreover, serum PGRN/tumour necrosis factor-α ratio was negatively correlated with disease severity. To investigate the role of PGRN in the pathogenesis of psoriasis, we used wild-type (WT) and PGRN(-/-) mice in a model of 12-O-tetradecanoylphorbol 13-acetate (TPA) -induced psoriasis-like inflammation. We demonstrated that PGRN expression was dramatically enhanced in the psoriasis-like lesions of TPA-treated WT mice, in accordance with human psoriatic lesions. Surprisingly, PGRN(-/-) mice were more sensitive to the development of TPA-induced psoriasis-like inflammation. The mechanism underlying this increased sensitivity of PGRN(-/-) mice to TPA-induced psoriasis-like inflammation was impaired differentiation of regulatory T cells in lymph nodes and decreased recruitment of these cells in the affected skin, which results in more severe inflammation. Hence, in WT mice, PGRN promotes differentiation and recruitment of regulatory T cells at the site of inflammation, which protects the skin from an exaggerated psoriasis-like inflammatory response.
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine designated by the Ministry of Education, Chongqing Medical University, Chongqing, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Huang
authors.forename: Aijun
authors.initials: A
authors.lastname: Chen
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhang
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Song
authors.forename: Hongmei
authors.initials: H
authors.lastname: Xu
authors.forename: Ju
authors.initials: J
authors.lastname: Cao
authors.forename: Yibing
authors.initials: Y
authors.lastname: Yin
mesh_terms: D000328:Adult; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D000077155:Granulins; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D000077153:Progranulins; D011565:Psoriasis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D012867:Skin / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D002273:Carcinogens; C492314:GRN protein, human; D000077155:Granulins; C120204:Grn protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; D013755:Tetradecanoylphorbol Acetate
keywords: inflammation; progranulin; psoriasis; regulatory T cells