Role of Interleukin 36 in Generalised Pustular Psoriasis and Beyond

Generalised pustular psoriasis (GPP), a severe neutrophilic skin disease characterised by the sudden and widespread eruption of superficial sterile pustules, remains a challenging disease with limited treatment options. The recent discovery of genetic mutations associated with GPP and advances in understanding of the molecular mechanisms of autoinflammation have resulted in identification of key cytokines that drive the development and progression of GPP. Accumulating evidence demonstrates that interleukin (IL)-36 acts as a central node cytokine by orchestrating the hyperactivation of key pro-inflammatory cytokines and stimulating immune cells, including neutrophilic accumulations, a unique feature of GPP skin lesions. These findings are paving the way for the discovery and development of novel targeted GPP therapeutics that block the IL-36 pathway and neutralise the pathogenic immunologic mechanisms and pro-inflammatory cytokines. This article provides an overview of the current evidence that supports the role of IL-36 as a central node cytokine in GPP pathogenesis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13555-021-00677-8.