The IL-20 receptor axis in immune-mediated inflammatory arthritis: novel links between innate immune recognition and bone homeostasis
The IL-20 receptor axis in immune-mediated inflammatory arthritis: novel links between innate immune recognition and bone homeostasis
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DOI：
10.1080/03009742.2016.1203022
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发表时间：
2016-01-01
影响因子：
2.1
通讯作者：
Kragstrup, T. W.
中科院分区：
文献类型：
--
作者：
Kragstrup, T. W.
类风湿性关节炎（RA）和脊柱关节炎（SpA）的治疗在十多年前通过引入中和促炎细胞因子肿瘤坏死因子（TNF）的试剂而改变。然而，一些患者没有达到缓解，并且当前药物对正常免疫系统的抑制增加了感染的风险。白细胞介素（IL）-20受体（IL-20 R）轴对于组织稳态是关键的。相反，这个轴似乎并不直接激活免疫系统的细胞。因此，IL-20 R轴的调节可能不会导致感染风险增加。IL-20 R轴由三种细胞因子IL-19、IL-20和IL-24（称为IL-20 R细胞因子）及其共享受体组成。3种细胞因子均与IL-20 R2/IL-20 R1受体复合物结合，而只有IL-20和IL-24与IL-20 R2/IL-22 R1受体复合物结合。本文就IL-20 R轴如何成为天然免疫识别与骨稳态之间的一种新的联系作一综述。IL-20 R细胞因子响应RA相关的分子模式和由RA相关的自身抗体形成的免疫复合物而产生。这可能是重要的，因为这些介质可以因此存在，即使在没有炎症的情况下。IL-19通过IL-20 R1在关节炎中显示抗炎特性。IL-20和IL-24通过IL-22 R似乎参与了单核细胞向滑膜关节的募集，特别是向骨侵蚀部位的募集。我们的结果表明，IL-20和IL-24的双重抑制或共享IL-22 R亚基的减弱可能对放射学进展产生有益影响，尤其是在血清阳性RA中。
The treatment of rheumatoid arthritis (RA) and spondyloarthritis (SpA) was transformed a little over a decade ago by the introduction of agents neutralizing the pro-inflammatory cytokine tumour necrosis factor (TNF)-. Nevertheless, some patients do not achieve remission and the inhibition of the normal immune system with current drugs increases the risk of infection.The interleukin (IL)-20 receptor (IL-20R) axis is pivotal for tissue homeostasis. By contrast, this axis does not seem to directly activate cells of the immune system. Thus, modulation of the IL-20R axis might not result in increased risk of infection. The IL-20R axis consists of the three cytokines IL-19, IL-20, and IL-24 (termed the IL-20R cytokines) and their shared receptors. All three cytokines bind the receptor complex of IL-20R2/IL-20R1 whereas only IL-20 and IL-24 also bind the receptor complex of IL-20R2/IL-22R1.This short review describes how the IL-20R axis could be a novel link between innate immune recognition and bone homeostasis. The IL-20R cytokines are produced in response to both danger-associated molecular patterns and immune complexes formed by RA-associated autoantibodies. This could be of importance because these mediators can thus be present even in situations without inflammation.IL-19 shows anti-inflammatory properties in arthritis through IL-20R1. IL-20 and IL-24 through IL-22R seem to participate in the recruitment of mononuclear cells to the synovial joint and to sites of bone erosion in particular. Our results indicate that dual inhibition of IL-20 and IL-24 or attenuation of the shared IL-22R subunit could have a beneficial effect on radiographic progression, especially in seropositive RA.