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Int J Mol Sci ; 22(13)2021 Jun 23.
Article in English | MEDLINE | ID: mdl-34201664

ABSTRACT

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.


Subject(s)
Psoriasis/drug therapy , Psoriasis/etiology , Receptors, Interleukin-17/physiology , Antibodies, Monoclonal, Humanized/pharmacology , Humans , Interleukin-17/immunology , Interleukin-17/metabolism , Protein Isoforms
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