From Messengers to Receptors in Psoriasis: The Role of IL-17RA in Disease and Treatment

International Journal of Molecular Sciences

Álvaro González-Cantero¹  Antonio-Manuel Velasco-Pastor²  José-Carlos Ruiz-Carrascosa³  José-Manuel Carrascosa-Carrillo⁴  Lluís Puig⁵  Silvia Vidal⁵ 

[1] Department of Dermatology, Hospital Universitario Ramón y Cajal, M-607, km. 9, 100, 28034 Madrid, Spain;Hospital Arnau de Vilanova, 46015 Valencia, Spain;Hospital Clínico Universitario San Cecilio, 18016 Granada, Spain;Hospital Germans Trias i Pujol, 08916 Badalona, Barcelona, Spain;Institute of Research, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain;

关键词: psoriasis;    Th17;    IL-17;    IL-17R;    monoclonal antibodies;    secukinumab;   

DOI  :  10.3390/ijms22136740

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown