C5a/C5aR1 Pathway Is Critical for the Pathogenesis of Psoriasis
C5a/C5aR1 Pathway Is Critical for the Pathogenesis of Psoriasis
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C5a/C5aR1 通路对于银屑病的发病机制至关重要
DOI：
10.3389/fimmu.2019.01866
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发表时间：
2019-08
期刊：
影响因子：
--
通讯作者：
Gui-lian Xu
中科院分区：
文献类型：
--
作者：
Quan-you Zheng;Shen-ju Liang;Feng Xu;Gui-qing Li;Na Luo;Shun Wu;You Li;Ming Tang;Yu Zhong;Jian Chen;Di Yang;Dao-dong Sun;Ke-qin Zhang;Gui-lian Xu
银屑病是最常见的慢性炎症性皮肤病之一，影响约2%的人口。银屑病的发病机制缺乏表征，阻碍了有效的临床治疗。在我们的研究中，我们观察到补体成分5a受体1（C5 aR 1）的表达在咪喹莫特（IMQ）和IL 23诱导的银屑病小鼠和银屑病患者的皮肤病变中显著增加。C5 aR 1缺陷或C5 a受体1拮抗剂（C5 aR 1a）治疗小鼠显著减弱银屑病样皮肤病变和炎性细胞因子和趋化因子的表达。此外，C5 aR 1缺陷显著降低了IMQ诱导的银屑病皮损中浆细胞样树突状细胞（pDC）、单核细胞和中性粒细胞的浸润以及pDC的功能，这通过IMQ诱导的干扰素-α（IFN-α）和肿瘤坏死因子-α（TNF-α）的产生以及FMS样酪氨酸激酶3配体（FLT 3L）依赖的pDC分化的显著降低来证明。因此，用重组C5 a体外处理加速了pDC迁移和骨髓细胞向pDC的分化。此外，与健康受试者相比，银屑病患者的活检显示银屑病皮肤病变中C5 aR 1 + pDC浸润显著增加。我们的研究结果提供了直接的证据，C5 a/C5 aR 1信号转导在银屑病的发病机制中起着至关重要的作用。C5 a/C5 aR 1通路的抑制预期在银屑病患者的治疗中是有益的。
Psoriasis is one of the most common chronic inflammatory skin diseases, affecting ~2% of the population. The lack of characterization of the pathogenesis of psoriasis has hindered efficient clinical treatment of the disease. In our study, we observed that expression of complement component 5a receptor 1(C5aR1) was significantly increased in skin lesions of both imiquimod (IMQ) and IL23-induced psoriatic mice and patients with psoriasis. C5aR1 deficiency or treatment with C5a receptor 1 antagonist (C5aR1a) in mice significantly attenuated psoriasis-like skin lesions and expression of inflammatory cytokines and chemokines. Moreover, C5aR1 deficiency significantly decreased IMQ-induced infiltration of plasmacytoid dendritic cells (pDCs), monocytes and neutrophils in psoriatic skin lesions and functions of pDCs, evidenced by the remarkable reduction in the IMQ-induced production of interferon-α (IFN-α) and tumor necrosis factor α (TNF-α), and FMS-like tyrosine kinase 3 ligand (FLT3L)-dependent pDCs differentiation. Accordingly, in vitro treatment with recombinant C5a accelerated pDCs migration and the differentiation of bone marrow cells into pDCs. Furthermore, biopsies of psoriatic patients showed a dramatic increase of C5aR1+ pDCs infiltration in psoriatic skin lesions, compared to healthy subjects. Our results provide direct evidence that C5a/C5aR1 signaling plays a critical role in the pathogenesis of psoriasis. Inhibition of C5a/C5aR1 pathway is expected to be beneficial in the treatment of patients with psoriasis.
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DOI：
10.1084/jem.20020045
发表时间：
2002-04-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gilliet M;Boonstra A;Paturel C;Antonenko S;Xu XL;Trinchieri G;O'Garra A;Liu YJ
通讯作者：
Liu YJ
DOI：
10.1111/j.1346-8138.2010.01037.x
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期刊：
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影响因子：
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作者：
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W. Boehncke;M. Schön
影响因子：
5.4
作者：
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通讯作者：
Nestle, Frank O.
影响因子：
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作者：
H. Takematsu;K. Ohkohchi;H. Tagami
通讯作者：
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DOI：
10.7326/0003-4819-155-3-201108020-01002
发表时间：
1906-04
期刊：
The Hospital
影响因子：
--
作者：
M. Lebwohl
通讯作者：
M. Lebwohl