The plot thickens while the scope broadens: a holistic view on IL-17 in psoriasis and other inflammatory disorders

Psoriasis is an instructive example highlighting our growing knowledge about pathophysiological functions of interleukin (IL)-17. IL-17A is the predominant isoform implicated in key pathogenic features in this and other chronic inflammatory disorders. Several monoclonal antibodies targeting IL-17A (secukinumab, ixekizumab) or its IL-17RC/RA receptor (brodalumab) are currently in late stages of clinical development, where they have shown impressive efficacy. While the eponymous IL-17 has been thought to originate primarily from T helper (Th)17 cells, more recent investigations by several groups suggest that other cell types in psoriatic lesions, such as neutrophils and mast cells, are rich sources of IL-17, thus presumably contributing to the disease process to an as yet underestimated extent. This recent paradigm shift provides a plausible explanation for the rapid and strong efficacy of the novel compounds targeting IL-17 functions in psoriasis and other inflammatory disorders, and provide a more comprehensive view on the complex cytokine network in these conditions.