Il36a
Function
Cytokine that binds to and signals through the IL1RL2/IL-36R receptor which in turn activates NF-kappa-B and MAPK signaling pathways in target cells linked to a pro-inflammatory response. Part of the IL-36 signaling system that is thought to be present in epithelial barriers and to take part in local inflammatory response; similar to the IL-1 system with which it shares the coreceptor IL1RAP. Seems to be involved in skin inflammatory response by acting on keratinocytes, dendritic cells and indirectly on T-cells to drive tissue infiltration, cell maturation and cell proliferation. Induces the production of pro-inflammatory cytokines, including IL-12, Il-1 beta, IL-6, TNF-alpha and IL-23 in bone marrow-derived dendritic cells (BMDCs). Involved in dendritic cell maturation by stimulating the surface expression of CD80, CD86 and MHC class II. Induces the production of IFN-gamma, IL-4 and IL-17 by cultured CD4(+) T-cells and splenocytes. May play a role in pro-inflammatory effects in the lung: induces the expression of CXCL1 and CXCL2 in the lung, and the expression of TNF-alpha, IL-36c, IL-1A, IL-1B, CXCL1 and CXCL2 in isolated splenic CD11c(+) alveolar macrophages. May be involved in T-cell maturation by stimulating the surface expression of CD40 and modestly CD80 and CD86 in splenic CD11c(+) cells. May be involved in CD4(+) T-cell proliferation. Induces NF-kappa B activation in macrophages.
Post-translational modifications
N-terminal truncation leads to a dramatic enhancement of its activity (>1000-fold).
Sequence Similarities
Belongs to the IL-1 family.
Tissue Specificity
Highly expressed in embryonic tissue and in tissues containing epithelial cells. Elevated expression levels are detected in chronic kidney disease; expressed inepithelia from the distal convoluted tubules (DCTs) to the cortical collecting ducts (CCDs) in single nephrons (at protein level).
Cellular localization
- Cytoplasm
- Secreted
- The secretion is dependent on protein unfolding and facilitated by the cargo receptor TMED10; it results in protein translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) followed by vesicle entry and secretion.
Alternative names
Fil1e, Il1e, Il1f6, Il1h1, Il36a, Interleukin-36 alpha, FIL1 epsilon, Interleukin-1 epsilon, Interleukin-1 family member 6, Interleukin-1 homolog 1, IL-1 epsilon, IL-1F6, IL-1H1