Psoriasis is a chronic, proliferative, and inflammatory skin disease closely associated with inflammatory cytokine production. Cyclophilin A (CypA) is an important proinflammatory factor; however, its role in psoriasis remains unclear. The present data indicate that CypA levels are increased in the lesion skin and serum of patients with psoriasis, which is positively correlated with the psoriasis area severity index. Furthermore, extracellular CypA (eCypA) triggered psoriasis-like inflammatory responses in keratinocytes. Moreover, anti-CypA mAb significantly reduced pathological injury, keratinocyte proliferation, cytokine expression in imiquimod-induced mice. Notably, the therapeutic effect of anti-CypA mAb was better than that of the clinically used anti-IL-17A mAb and methotrexate. Mechanistically, eCypA binds to ACE2 and CD147 and is blocked by anti-CypA mAb. eCypA not only induces the dimerization and phosphorylation of ACE2 to trigger the JAK1/STAT3 signaling pathway for cytokine expression but also interacts with CD147 to promote PI3K/AKT/mTOR signaling-mediated keratinocyte proliferation. These findings demonstrate that the binding of eCypA to ACE2 and CD147 cooperatively triggers psoriasis-like inflammation and anti-CypA mAb is a promising candidate for the treatment of psoriasis.
基金:
National Key Research and Development Program of China [2023YFC2308600]; National Natural Science Foundation of China [32200711, 32372986, 32300145]
第一作者机构:[1]Shenzhen Bay Lab, Inst Infect Dis, Shenzhen 518107, Guangdong, Peoples R China[2]Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing 100101, Peoples R China[3]Capital Med Univ, Beijing Tongren Hosp, Beijing Ophthalmol & Visual Sci Key Lab, Beijing Inst Ophthalmol,Beijing Tongren Eye Ctr, Beijing 100730, Peoples R China
共同第一作者:
通讯作者:
通讯机构:[2]Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing 100101, Peoples R China[4]Univ Chinese Acad Sci, Savaid Med Sch, Beijing 100049, Peoples R China
推荐引用方式(GB/T 7714):
Yang Wenxian,Bai Xiaoyuan,Jia Xiaoxiao,et al.The binding of extracellular cyclophilin A to ACE2 and CD147 triggers psoriasis-like inflammation[J].JOURNAL OF AUTOIMMUNITY.2024,148:doi:10.1016/j.jaut.2024.103293.
APA:
Yang, Wenxian,Bai, Xiaoyuan,Jia, Xiaoxiao,Li, Huizi,Min, Jie...&Sun, Lei.(2024).The binding of extracellular cyclophilin A to ACE2 and CD147 triggers psoriasis-like inflammation.JOURNAL OF AUTOIMMUNITY,148,
MLA:
Yang, Wenxian,et al."The binding of extracellular cyclophilin A to ACE2 and CD147 triggers psoriasis-like inflammation".JOURNAL OF AUTOIMMUNITY 148.(2024)