IL-36α Protein, Mouse

Interleukin-36α (IL-36α, formerly IL-1F6) is a pro-inflammatory member of the IL-1 super-family. The mature mouse protein is an 18 kDa, 160-amino-acid, β-trefoil monomer that lacks a signal peptide and glycosylation sites. Full-length IL-36α is only weakly active; removal of the N-terminal methionine by neutrophil proteases (cathepsin G, elastase, proteinase-3) generates the highly active form. In mice, IL-36α mRNA is constitutively detected in skin keratinocytes, stomach, trachea, fetal brain, spleen, lymph nodes, kidney tubules and adipose tissue, and is rapidly up-regulated after TLR4 ligation, IL-1β, TNF-α or fungal challenge. Once released (passively during necrosis or through P2X7-dependent externalisation), IL-36α binds the heterodimeric receptor IL-1Rrp2/IL-1RAcP expressed on keratinocytes, dendritic cells, macrophages and CD4⁺ T cells. Engagement activates MyD88 → NF-κB and MAPKs (p38, JNK, ERK), leading to transcription of IL-6, IL-23, TNF-α, CXCL1, CXCL2, CCL3, β-defensin-3 and GM-CSF, and thereby amplifies Th1/Th17 immunity while recruiting neutrophils and monocytes.