The Th17 axis in psoriatic disease: pathogenetic and therapeutic implications.

Abstract

Psoriasis and psoriatic arthritis represent two paradigmatic conditions characterized by chronic inflammation and possibly autoimmunity, despite the absence of known serum autoantibodies. The two diseases, albeit strongly correlated from clinical, genetic, and epidemiogical standpoints, manifest significant differences in terms of etiology and pathogenetic mechanisms. Nonetheless, Th17 cells appear crucial to both diseases, and IL23 is the cytokine involved in determining the fate of naive CD4+ cells to differentiate into a pathogenic phenotype. This basic experimental observation led to a clear understanding of the immune dysfunction causing psoriasis and psoriatic arthritis but, more importantly, also led to new therapeutic approaches. In recent years, monoclonal antibodies directed to IL12/IL23 (ustekinumab) or IL17 (secukinumab, ixekizumab, brodalumab) are being investigated or have proven to be beneficial for patients with psoriatic disease, thus further supporting the view that Th17 cells play a pivotal role in disease onset and perpetuation. These most recent reports indeed represent significant developments that may allow overcoming the TNFα pathway as the major therapeutic target in chronic inflammation.