IL-36γ Protein, Mouse

Interleukin-36γ (IL-36γ, formerly IL-1F9) is the most intensively studied agonist of the IL-36 sub-family within the IL-1 cytokine super-family. The mature mouse protein is a 17–18 kDa, non-glycosylated, β-trefoil monomer that lacks both a signal peptide and a pro-domain; maximal bio-activity is gained after N-terminal truncation by neutrophil proteases. In the mouse, IL-36γ is constitutively produced by keratinocytes, Langerhans cells, gastric chief/parietal cells and lung epithelium, positioning it as a front-line alarmin at barrier surfaces. Transcription is rapidly up-regulated by TLR3/4 ligands, IL-1α/β, TNF-α or IL-17, and the cytokine is released passively during pyroptosis or necroptosis. Once in the extracellular space, IL-36γ engages the heterodimeric receptor complex IL-1Rrp2/IL-1RAcP expressed on keratinocytes, dendritic cells and macrophages, driving MyD88-dependent activation of NF-κB and MAPKs (p38, JNK, ERK). The ensuing transcriptional programme includes IL-6, IL-23, TNF-α, CXCL1, CXCL2, CXCL8 and β-defensin-3, translating into neutrophil influx, Th1/Th17 polarisation and antimicrobial peptide release.