The IL-20 Cytokine Family in Rheumatoid Arthritis and Spondyloarthritis.
The IL-20 Cytokine Family in Rheumatoid Arthritis and Spondyloarthritis.
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IL-20细胞因子家族在类风湿关节炎和脊柱性关节炎中的作用
DOI：
10.3389/fimmu.2018.02226
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发表时间：
2018
影响因子：
7.3
通讯作者：
Deleuran B
中科院分区：
文献类型：
--
作者：
Kragstrup TW;Andersen T;Heftdal LD;Hvid M;Gerwien J;Sivakumar P;Taylor PC;Senolt L;Deleuran B
本文综述了IL-20家族细胞因子在类风湿性关节炎(RA)和脊柱性关节炎(SpA)包括银屑病关节炎中的作用。IL-20受体(R)细胞因子IL-19、IL-20和IL-24在外周血和滑膜关节中产生，并由Toll样受体配体和单核细胞中自身抗体相关免疫复合物诱导。IL-19似乎在关节炎中具有抗炎作用。相反，IL-20和IL-24增加了促炎分子的产生，如单核细胞趋化蛋白1，并与骨骼退化和放射学进展有关。IL-22也与骨质侵蚀的进展有关。这表明IL-20、IL-22和IL-24所共有的IL-22Ra1亚基对骨稳态具有重要作用。与此相一致的是，在早期RA的破骨前细胞上发现了IL-22Ra1。IL-26由肌成纤维细胞大量产生，单核细胞刺激IL-26是RA患者Th17细胞的重要诱导物。这表明IL-26在常驻滑膜细胞和浸润性白细胞之间的相互作用中起着重要的作用。研究IL-20(Fletikumab)和IL-22(Fezakinumab)抑制剂治疗牛皮癣和RA的临床试验已经终止。相反，似乎调节IL-20细胞因子家族的策略应该考虑到细胞来源和效应机制的重叠。这种冗余鼓励抑制一个以上的细胞因子或一个共享的受体。所有IL-20家族成员都利用Janus激酶信号通路，因此可能会被针对这些酶的药物抑制。正在进行的IL-22、IL-22Ra1亚基和重组IL-22融合蛋白的临床试验的效果和不良反应可能会为未来提供有关IL-20亚家族的重要信息。
This review describes the IL-20 family of cytokines in rheumatoid arthritis (RA) and spondyloartrhitits (SpA) including psoriatic arthritis. The IL-20 receptor (R) cytokines IL-19, IL-20, and IL-24 are produced in both the peripheral blood and the synovial joint and are induced by Toll-like receptor ligands and autoantibody-associated immune complexes in monocytes. IL-19 seems to have anti-inflammatory functions in arthritis. In contrast, IL-20 and IL-24 increase the production of proinflammatory molecules such as monocyte chemoattractant protein 1 and are associated with bone degradation and radiographic progression. IL-22 is also associated with progression of bone erosions. This suggests that the IL-22RA1 subunit shared by IL-20, IL-22, and IL-24 is important for bone homeostasis. In line with this, the IL-22RA1 has been found on preosteoclasts in early RA. IL-26 is produced in high amounts by myofibroblasts and IL-26 stimulation of monocytes is an important inducer of Th17 cells in RA. This indicates a role for IL-26 as an important factor in the interactions between resident synovial cells and infiltrating leukocytes. Clinical trials that investigate inhibitors of IL-20 (fletikumab) and IL-22 (fezakinumab) in psoriasis and RA have been terminated. Instead, it seems that the strategy for modulating the IL-20 cytokine family should take the overlap in cellular sources and effector mechanisms into account. The redundancy encourages inhibition of more than one cytokine or one of the shared receptors. All IL-20 family members utilize the Janus kinase signaling pathway and are therefore potentially inhibited by drugs targeting these enzymes. Effects and adverse effects in ongoing clinical trials with inhibitors of IL-22 and the IL-22RA1 subunit and recombinant IL-22 fusion proteins will possibly provide important information about the IL-20 subfamily of cytokines in the future.
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影响因子：
4.4
作者：
Andoh, Akira;Shioya, Makoto;Fujiyama, Yoshihide
通讯作者：
Fujiyama, Yoshihide
影响因子：
30.5
作者：
Duhen, Thomas;Geiger, Rebekka;Sallusto, Federica
通讯作者：
Sallusto, Federica
DOI：
10.1084/jem.20060244
发表时间：
2006-11-27
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chan JR;Blumenschein W;Murphy E;Diveu C;Wiekowski M;Abbondanzo S;Lucian L;Geissler R;Brodie S;Kimball AB;Gorman DM;Smith K;de Waal Malefyt R;Kastelein RA;McClanahan TK;Bowman EP
通讯作者：
Bowman EP
影响因子：
168.9
作者：
Dougados, Maxime;Baeten, Dominique
通讯作者：
Baeten, Dominique
影响因子：
3.8
作者：
Buzas, Krisztina;Oppenheim, Joost J.;Howard, O. M. Zack
通讯作者：
Howard, O. M. Zack