PRELP negatively regulate IL-17A mediated proliferation and inflammatory in psoriasis
Cong-cong He,Rui-qun Qi,Xing-Hua Gao
Department of Dermatology, The First Hospital of China Medical University and Key Laboratory of Immunodermatology, Ministry of Health and Ministry of Education, Shenyang, Liaoning
Psoriasis is a common immune-mediated skin disease and IL-17A plays an important role in the pathogenesis of psoriasis. In this study, differentially expressed genes in three anti-IL-17A biologics(secukinumab, ixekizumab and brodalumab) treating psoriasis have been identified, those genes intersected with genes differentially expressed in psoriasis lesional versus non-lesional tissues. Then function of those genes analyzed and hub genes screened out. To verify expression of those hub genes, imiquimod induced psoriasis model in mouse and IL-17A treated hacat cells as well as lesions from psoriasis patients were used. PRELP were identified low expressed in psoriasis lesions both in patients and mouse model. What’s more, it’s expression also decreased after IL-17A treatment in the level of mRNA and protein in hacat cell. Functional experiments also been performed to explore role of PRELP in psoriasis. Over expression of PRELP inhibited proliferation and promoted apoptosis of hacat cells. Also, PRELP could inhibit IL-17A mediated NF-κB and MAPK signal as well as release of cytokines related to psoriasis including TNF-α and IL-1β. Inhibition of PRELP in skin also exacerbated psoriasis in mouse. Datasets analysis also found PRELP related effective therapeutic response in psoriasis patients treated with brodalumab and methotrexate but not etanercept and ustekinumab. Mechanically, IL-17A decreased expression of PRELP through induced STAT3, which is the transcription factor that negatively regulated transcription of PRELP. In conclusion, PRELP is a negative regulator in IL-17A mediated signal in psoriasis, it not only involved in the pathogenesis of psoriasis, but also related to the therapeutic response of anti-IL-17A biologics. Our study provide new ideas of pathogenesis and treatment target of psoriasis.
