Skin is the largest organ in the body and it serves as a protective barrier. It is made up of an outermost epidermal layer and an underlying dermal layer (Fig 1). The formation and maintenance of the epidermis depend on the precise regulation of keratinocyte proliferation, differentiation and apoptosis. This homeostasis relies on the network of cytokines and growth factors. Perturbation of this homeostasis leads to inflammatory skin diseases and cancer development. Interleukin-1 (IL-1) is a pro-inflammatory cytokine that is constitutively produced by keratinocytes. It is also involved in the proliferation and differentiation of keratinocytes. IL-1 binds to its cognate receptor and can trigger downstream pathways with different outcomes. sIL-1ra binds to IL-1 receptor and prevents the transmission of intracellular response. However, the phenotype of human epidermis when the underlying fibroblast cells is deficient of sIL-1ra remains unclear. [3rd Awards]