Center for Biophysical Sciences, University of Alabama, Birmingham, AL 35294, USA.
Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12704-9. doi: 10.1073/pnas.1117551109. Epub 2012 Jul 16.
Interleukin 20 (IL-20) is a pleotropic IL-10 family cytokine that protects epithelial surfaces from pathogens. However, dysregulated IL-20 signaling is implicated in several human pathologies including psoriasis, rheumatoid arthritis, atherosclerosis, and osteoporosis. IL-20, and related cytokines IL-19 and IL-24, designated IL-20 subfamily cytokines (IL-20SFCs), induce cellular responses through an IL-20R1/IL-20R2 (type I) receptor heterodimer, whereas IL-20 and IL-24 also signal through the IL-22R1/IL-20R2 (type II) receptor complex. The crystal structure of the IL-20/IL-20R1/IL-20R2 complex reveals how type I and II complexes discriminate cognate from noncognate ligands. The structure also defines how the receptor-cytokine interfaces are affinity tuned to allow distinct signaling through a receptor complex shared by three different ligands. Our results provide unique insights into the complexity of IL-20SFC signaling that may be critical in the design of mechanistic-based inhibitors of IL-20SFC-mediated inflammatory disease.
白细胞介素 20（IL-20）是一种多功能白细胞介素 10 家族细胞因子，可保护上皮表面免受病原体侵害。然而，IL-20 信号的失调与几种人类病理有关，包括银屑病、类风湿关节炎、动脉粥样硬化和骨质疏松症。白细胞介素 20、相关细胞因子白细胞介素 19 和白细胞介素 24 被指定为白细胞介素 20 亚家族细胞因子（IL-20SFC），通过白细胞介素 20R1/白细胞介素 20R2（I 型）受体异二聚体诱导细胞反应，而白细胞介素 20 和白细胞介素 24 也通过白细胞介素 22R1/白细胞介素 20R2（II 型）受体复合物信号传导。IL-20/IL-20R1/IL-20R2 复合物的晶体结构揭示了 I 型和 II 型复合物如何区分同源和非同源配体。该结构还定义了受体-细胞因子界面如何通过三个不同配体共享的受体复合物进行亲和力调谐，以允许通过独特的信号转导。我们的研究结果提供了对 IL-20SFC 信号转导复杂性的独特见解，这对于设计基于机制的 IL-20SFC 介导的炎症性疾病抑制剂可能至关重要。
