Human Interleukin 31 (IL-31) is a cytokine containing a four-helix bundle structure. It shares several structural and functional characteristics with IL-6, Oncostatin M, LIF, and Cardiotrophin-1. Human IL-31 cDNA encodes a 164 amino acid precursor that contains a 23 amino acid signal peptide and a 141 amino acid mature protein. Human and mouse IL-31 share 24% sequence identity in the mature region. IL-31 is mainly associated with activated T cells and is preferentially expressed by type 2 helper T cells (Th2). IL-31 signals via a heterodimeric receptor complex composed of a gp130 related molecule termed IL-31RA (also GPL and GLMR) and an Oncostatin M receptor (OSM Rβ). The IL-31 receptor is constitutively expressed by keratinocytes and upregulated by IFNγ on monocytes. GPL/OSMR signaling is a strong activator of STAT3 and STAT5, and can also activate STAT1, Jak1, and Jak2 signaling pathways. IL-31 regulated immune responses have been implicated in skin physiology and inflammatory skin diseases. Studies have shown that IL31 induces severe pruritis (itching) and dermatitis in transgenic mice.
Interleukin-33 (IL-33) was initially discovered as a nuclear factor NF-HEV abundantly expressed in high endothelial venules. It is a 30-32 kD pro-inflammatory protein with intracellular and extracellular activities and a chromatin-associated cytokine of the IL-1 family with high sequence and structural similarity to IL-1 and IL-18. IL-33 is highly and selectively expressed by high endothelial venule endothelial cells (HEVECs) in human tonsils; Peyers's patches; and lymph nodes. It contains a bipartite nuclear localization signal at the C-terminus; and is targeted to the nucleus when ectopically expressed in human umbilical vein endothelial cells (HUVECs) and HeLa cells. The C-terminal fragment; corresponding to mature IL-33; binds and triggers signaling. IL-33 mediates its biological effects via Toll-interleukin 1 (IL-1) receptor (TIR) domain-containing receptor ST2; activates NF-kappaB and MAP kinases; and drives production of T(H)2-associated cytokines from in vitro polarized T(H)2 cells. In vivo; IL-33 induces the expression of IL-4; IL-5; and IL-13 and leads to severe pathological changes in mucosal organs. Human IL-33 is 270 amino acids in length.
Interleukin-33 (IL-33) belongs to the IL-1 superfamily. IL33 is highly expressed in endothelial venules found in tonsils; Peyer patches and mesenteric lymph nodes; but almost undetectable in placenta. IL33 induces the production of T helper-2 (Th2)-associated cytokines. IL-33 is a cytokine that mediates its biological effects by binding to and signals through IL1RL1/ST2 and IL-1 Receptor Accessory Protein (IL1RAP); activating intracellular molecules in the NF-κB and MAP kinase signaling pathways that drive production of type 2 cytokines from polarized Th2 cells.
Human Interleukin-36α (IL-36α) is a secreted cytokine that belongs to the Interleukin 1 cytokine family. IL-36α is expressed in the immune system and the fetal brain, but not in other tissues or multiple hematopoietic cell lines. IL-36α is the only IL-1 family member found to be expressed on T-cells. IL-36α and IL-1F8 are involved in the regulation of adipose tissue gene expression. Importantly, IL-36α inhibits PPARγ expression, which may lead to a reduction in adipocyte differentiation suggesting metabolic effects of this cytokine. IL-36α, along with IL-1F8 and IL-1F9, has been shown to act as an agonist by activating the pathway involving NFκB and MAPK in an IL-1Rrp2 dependent manner. This suggest that IL-36α may signal in a similar fashion to IL-1 and IL-18 in having a binding receptor which upon ligation, recruits a second receptor as a signaling component, forming an active heterodimeric receptor complex.
Interleukin-3 (IL-3) is a potent growth promoting cytokine. IL-3 can stimulate the proliferation and differentiation of pluripotent hematopoietic stem cells as well as various lineage committed progenitors. IL-3 exerts its biological function through binding to specific cell surface receptors. The amino acid sequences of this protein among different species share relatively low identity and its activity is highly species-specific. IL-3 has also been shown to possess neurotrophic activity; and is thought to be associated with neurologic disorders.
Interleukin-3 (IL-3) is a potent growth promoting cytokine. IL-3 can stimulate the proliferation and differentiation of pluripotent hematopoietic stem cells as well as various lineage committed progenitors. IL-3 exerts its biological function through binding to specific cell surface receptors. The amino acid sequences of this protein among different species share relatively low identity and its activity is highly species-specific. IL-3 has also been shown to possess neurotrophic activity, and is thought to be associated with neurologic disorders.
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