IL36RN Protein

Background

IL36RN, also known as IL-36Ra, is an anti-inflammatory cytokine that functions as a natural inhibitor of IL-36 signaling. It binds to the IL-36 receptor (IL1RL2) and prevents its activation by IL36A, IL36B, and IL36G, thereby blocking downstream NF-κB, MAPK, and JNK signaling pathways. IL36RN is primarily expressed in keratinocytes, epithelial cells, and immune cells, where it regulates inflammation and prevents excessive immune activation at epithelial barriers. It plays a key role in maintaining tissue homeostasis and limiting pathological inflammation in conditions such as psoriasis, where mutations in IL36RN lead to uncontrolled IL-36 activity, severe inflammation, and pustular psoriasis. IL36RN is also implicated in mucosal immunity and inflammatory diseases of the skin, lungs, and gastrointestinal tract. Knockout studies reveal heightened IL-36 signaling, excessive cytokine production, and severe tissue inflammation, underscoring IL36RN's role as a key anti-inflammatory regulator and protective factor in immune homeostasis and barrier tissue health.