Interleukin-17 receptor D constitutes an alternative receptor for interleukin-17A important in psoriasis-like skin inflammation

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Science Immunology  07 Jun 2019:
Vol. 4, Issue 36, eaau9657
DOI: 10.1126/sciimmunol.aau9657

A new receptor for interleukin-17

The cytokines interleukin-17A (IL-17A) and IL-17F drive immune activation by binding to the IL-17 receptor (IL-17R) complex composed of two subunits, IL-17RA and IL-17RC. Here, Su et al. identify a second IL-17R complex composed of IL-17RA and IL-17RD that is expressed by skin keratinocytes. Using a mouse model of psoriasis, they report that IL-17RA/IL-17RD complex plays a vital role in driving IL-17–dependent skin inflammation. Although the IL-17RA/IL-17RC complex binds IL-17A and IL-17F homodimers and IL-17A/IL-17F heterodimers, they report here that the IL-17RA/IL-17RD specifically binds IL-17A homodimers. As antibodies targeting IL-17 cytokines and their receptors are being used in the treatment of autoimmune diseases, the discovery of a second receptor is interesting from both basic and clinical viewpoints.