Institute of Research, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain.
Hospital Germans Trias i Pujol, 08916 Badalona, Barcelona, Spain.
Int J Mol Sci. 2021 Jun 23;22(13):6740. doi: 10.3390/ijms22136740.
The paradigm of psoriasis as a Th17-driven disease has evolved in the last years towards a much deeper knowledge of the complex pathways, mechanisms, cells, and messengers involved, highlighting the crucial role played by the IL-17 family of cytokines. All IL-17 isoforms signal through IL-17R. Five subunits of IL-17R have been described to date, which couple to form a homo- or hetero-receptor complex. Characteristically, IL-17RA is a common subunit in all hetero-receptors. IL-17RA has unique structural-containing a SEFIR/TILL domain-and functional-requiring ACT-1 for signaling-properties, enabling Th17 cells to act as a bridge between innate and adaptive immune cells. In psoriasis, IL-17RA plays a key role in pathogenesis based on: (a) IL-17A, IL-17F, and other IL-17 isoforms are involved in disease development; and (b) IL-17RA is essential for signaling of all IL-17 cytokines but IL-17D, whose receptor has not been identified to date. This article reviews current evidence on the biology and role of the IL-17 family of cytokines and receptors, with focus on IL-17RA, in psoriasis and some related comorbidities, and puts them in context with current and upcoming treatments.
近年来，银屑病作为一种由 Th17 驱动的疾病的范式已经发展为对涉及的复杂途径、机制、细胞和信使有了更深入的了解，突出了细胞因子 IL-17 家族的关键作用。所有的 IL-17 同种型都通过 IL-17R 信号传递。迄今为止，已经描述了 5 种 IL-17R 的亚基，它们可以形成同源或异源受体复合物。特征上，IL-17RA 是所有异源受体中的共同亚基。IL-17RA 具有独特的结构，包含 SEFIR/TILL 结构域和功能，需要 ACT-1 进行信号转导，使 Th17 细胞能够在先天和适应性免疫细胞之间发挥桥梁作用。在银屑病中，IL-17RA 在发病机制中起着关键作用，基于：(a)IL-17A、IL-17F 和其他 IL-17 同种型参与疾病的发展；和(b)IL-17RA 是所有 IL-17 细胞因子但 IL-17D 信号转导所必需的，其受体迄今尚未确定。本文综述了目前关于细胞因子和受体的 IL-17 家族的生物学和作用的证据，重点是 IL-17RA 在银屑病和一些相关并发症中的作用，并将其与当前和即将出现的治疗方法联系起来。
