Fig. 3

Main IL-18/IL-36 pathway defect-inducing autoinflammatory disorders classified according to pathophysiology. Pyrin function is modulated by cytoskeleton formation, especially the actin polymerization/depolymerization process, which is regulated by WDR1 function. This process mainly induces the IL-18-producing inflammasome, similar to the NLRC4 inflammasome. The IL-18/IL-36 pathway is critical for keratinocyte formation. Extracellular modulation of the IL-36 pathway is mainly modulated by IL-36RA, and intracellular signaling is mediated by CARD14-induced NF-κB. Red squares depict the main syndromes and their respective molecular targets classified as gain-of-function (continuous line) and loss-of-function (dashed line)-causing mutations. CAMPS (CARD14-mediated psoriasis); CARD14 (caspase recruitment domain family member 14); DITRA (deficiency of IL-36RA); GOF (gain-of-function); IL-36RA (IL-36 receptor antagonist); NAD (NLRP4 autoinflammatory disease); NLRP4 (NLR family CARD domain containing 4); PFIT (autoinflammatory periodic fever, immunodeficiency, and thrombocytopenia); WDR1 (WD repeat-containing protein 1)