Table 3.

Overview of the IL-1 family members involved in GPP pathogenesis

Cytokine	Receptor	Role in GPP pathogenesis
IL-1β	IL-1R1	IL-1β paracrine signalling network activates pro-inflammatory pathways [10]
IL-18	IL-18Ra	IL-18, a component of the inflammasomes expressed in epidermal keratinocyte, activates the paracrine pro-inflammatory signalling network in the epidermis and the superficial dermis [10]
IL-36α IL-36β IL-36γ	IL-36R (IL-1Rrp2)	The secretion of IL-36 by the keratinocyte results in the activation of neutrophils and dendritic cells in the dermis. Additionally, autocrine stimulation of keratinocytes results in the secretion of IL-36, IL-8, CXCL1, CXCL2 and CCL20, which further activates pro-inflammatory pathways [10]
IL-38	IL-36R (IL-1Rrp2)	IL-38 is a 17–18 kDa protein that shares 40% sequence similarity with IL-1Ra and IL-36Ra (antagonists of IL-1 and IL-36, respectively) and binds IL-36R to antagonise IL-36. IL-38 is expressed mainly in the skin and immune cells, and its expression is downregulated by inflammatory cytokines [70]
IL-1Ra	IL-1R1	Loss-of-function mutations in IL1RN, which encodes IL-1Ra, lead to a partial or complete absence of the IL-1Ra protein, causing uncontrolled activity of IL-1α and IL-1β [71, 72]
IL-36Ra	IL-36R	Deficiency in IL-36Ra caused by IL36RN loss-of-function mutations is thought to result in acceleration of IL-36-driven skin inflammation [10]

IL, interleukin