IL36B (interleukin-36 beta) is a pro-inflammatory cytokine member of the IL-1 family that signals through the IL-36R receptor heterodimer to activate NF-κB and MAPK pathways 1. It is primarily expressed at barrier sites including skin, lungs, and intestines, where it plays a vital role in local inflammatory responses 1. In keratinocytes, IL36B induces production of chemokines (CCL20, CXCL8, CCL5) and pro-inflammatory cytokines, driving recruitment and activation of innate immune cells including neutrophils and dendritic cells, and adaptive immune responses via Th1 and Th17 cells 1. IL36B is significantly upregulated during inflammatory skin conditions and is decreased during periodontitis lesion resolution 2. The cytokine is critical for cutaneous immunity against herpes simplex virus infections, with IL36B expression decreasing in Pellino1-deficient mice showing impaired epidermal immune responses 3. Dysregulation of IL36B contributes to pathogenesis of psoriasis, atopic dermatitis, hidradenitis suppurativa, and neutrophilic dermatoses through aberrant innate immune activation 14. Elevated IL36B levels correlate with severe COVID-19 disease outcomes 5, and IL36B has been identified as an immune-related prognostic gene in uveal melanoma 6. The IL-36/IL-36R axis represents a promising therapeutic target for inflammatory disorders.