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Progranulin is preferentially expressed in patients with psoriasis vulgaris and protects mice from psoriasis‐like skin inflammation
Author(s) -
Huang Kun,
Chen Aijun,
Zhang Xuemei,
Song Zhixin,
Xu Hongmei,
Cao Ju,
Yin Yibing
Publication year - 2015
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12446
Subject(s) - psoriasis , inflammation , tumor necrosis factor alpha , pathogenesis , medicine , immunology , lymph , pathology
Summary 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.