Cytokines & Chemokines

Interleukin-2(IL-2) is an interleukin; a type of cytokine signaling molecule in the immune system;belongs to the IL-2 family. It is a powerful immunoregulatory lymphokine produced by T-cells in response to antigenic or mitogenic stimulation. IL-2/IL-2R signaling is required for T-cell proliferation and other fundamental functions that are essential for the immune response. IL-2 stimulates growth and differentiation of B-cells; NK cells; lymphokine-activated killer cells; monocytes; macrophages and oligodendrocytes.

Interleukin-4 (IL-4) is a pleiotropic cytokine that regulates diverse T and B cell responses including cell proliferation; survival and gene expression. IL-4 is produced by mast cells; T cells; and bone marrow stromal cells. IL-4 regulates the differentiation of naive CD4+ T cells into helper Th2 cells; characterized by their cytokine-secretion profile that includes secretion of IL-4; IL-5; IL-6; IL-10; and IL-13; which favor a humoral immune response. Another dominant function of IL-4 is the regulation of immunoglobulin class switching to the IgG1 and IgE isotypes. Excessive IL-4 production by Th2 cells has been associated with elevated IgE production and allergic response.

The Interleukin-17 family proteins, comprising six members (IL-17, IL-17B through IL-17F),are secreted, structurally related proteins that share a conserved cysteine-knot fold near the C-terminus, but have considerable sequence divergence at the N-terminus. IL-17 family proteins are proinflammatory cytokines that induce local cytokine production and are involved in the regulation of immune functions. Among IL-17 family members, IL-17D is most closely related to IL-17B, sharing 27% aa sequence homology. IL-17D is expressed preferentially in skeletal muscle, heart, adipose tissue, lung, pancreas, and nervous system. Like other IL-17 family members, IL-17D modulates immune responses indirectly by stimulating the production of myeloid growth factors and chemokines including IL-6, IL-8, and GM-CSF. IL-17D has also been shown to suppress the proliferation of myeloid progenitors in colony formation assays.

Mouse IL-12 is a heterodimeric pleiotropic cytokine made up of a 40 kDa (p40) subunit and a 35 kDa (p35) subunit. Human and mouse IL-12 share 70% and 60% amino acid sequence identity in their p40 and p35 subunits, respectively. While mouse IL-12 is active on both human and mouse cells, human IL-12 is not active on murine cells. It is involved in the differentiation of naive T cells into Th1 cells. It is known as a T cell-stimulating factor, which can stimulate the growth and function of T cells. It stimulates the production of interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) from T cells and natural killer (NK) cells, and reduces IL-4 mediated suppression of IFN-γ. T cells that produce IL-12 have a coreceptor, CD30, which is associated with IL-12 activity. IL-12 plays an important role in the activities of natural killer cells and T lymphocytes.IL-12 mediates enhancement of the cytotoxic activity of NK cells and CD8+ cytotoxic T lymphocytes.

Interleukin-17F (IL-17F) exists in a disulfide-linked heterodimer that belongs to the IL-17 family. IL-17F is expressed in activated, but not resting, CD4+ T-cells and activated monocytes. Mouse and human IL-17F share 55% sequence identity.IL-17F has been shown to stimulate the production of several other cytokines, including IL-6, IL-8, and granulocyte colony-stimulating factor. IL-17F can regulate cartilage matrix turnover and stimulates PBMC and T-cell proliferation. IL-17F is also found to inhibit the angiogenesis of endothelial cells and induce endothelial cells to produce IL2, TGFB1/TGFB, and monocyte chemoattractant protein-1. Defects in IL-17F are the cause of familial candidiasis type 6 (CANDF6).

Interleukin-22 (IL-22) was initially identified as a gene induced by IL-9 in mouse T cells and mast cells. Mouse IL-22 cDNA encodes a 179 amino acid residue protein with a putative 33 amino acid signal peptide that is cleaved to generate a 147 amino acid mature protein that shares approximately 79% and 22% sequence identity with human IL22 and IL10, respectively. IL22 has been shown to activate STAT-1 and STAT-3 in several hepatoma cell lines and up-regulate the production of acute phase proteins. IL-22 is produced by normal mouse T cells upon Con A activation. Mouse IL-22 expression is also induced in various organs upon lipopolysaccharide injection, suggesting that IL-22 may be involved in inflammatory responses. The functional IL-22 receptor complex consists of two receptor subunits, IL-22R (previously an orphan receptor named CRF2-9) and IL-10Rβ (previously known as CRF2-4), belonging to the class II cytokine receptor family.

IL-27 is a heterodimeric cytokine which belongs to the IL-6/IL-12 family of long type I cytokines. It is expressed on monocytes, endothelial cells and dendritic cells. IL-27 is an early product of activated antigen-presenting cells and drives rapid clonal expansion of naive CD4(+) T cells and plays a role in the early regulation of Th1 cells initiation which drives efficient adaptive immune response. IL-27 potentiates the early phase of TH1 response and suppresses TH2 and TH17 differentiation. It induces the differentiation of TH1 cells via two distinct pathways, p38 MAPK/TBX21- and ICAM1/ITGAL/ERK-dependent pathways. It also induces STAT1, STAT3, STAT4 and STAT5 phosphorylation and activates TBX21/T-Bet via STAT1 with resulting IL12RB2 up-regulation, an event crucial to TH1 cell commitment. IL-27 reveals to be a potent inhibitor of TH17 cell development and of IL-17 production. Indeed IL27 alone is also able to inhibit the production of IL17 by CD4 and CD8 T-cells. IL-27 has also an e

Mouse Interleukin-4(IL-4) is a monomeric, Th2 cytokine that shows pleiotropic effects during immune responses. It is a glycosylated polypeptide that contains three intrachain disulfide bridges and adopts a bundled four α-helix structure. IL-4 exerts its effects through two receptor complexes, Participates in at least several B-cell activation processes as well as of other cell types. IL-4 is primarily expressed by Th2-biased CD4+T cells, mast cells, basophils, and eosinophils. It promotes cell proliferation, survival, and immunoglobulin class switch to IgG1 and IgE in mouse B cells, acquisition of the Th2 phenotype by na?ve CD4+T cells, priming and chemotaxis of mast cells, eosinophils, and basophils, and the proliferation and activation of epithelial cells. IL-4 plays a dominant role in the development of allergic inflammation and asthma. It also regulates the expression of the low affinity Fc receptor for IgE (CD23) on both lymphocytes and monocytes.

Mouse interleukin 13 (mIL-13) is a pleiotropic cytokine produced by activated Th2 cells. IL-13 induces B cell proliferation and immunoglobin production. It contains a four helical bundle with two internal disulfide bonds. Mouse IL13 shares 58% sequence identity with human protein and exhibits cross-species activity. IL13 signals via receptor IL13R (type2, IL4R) and activates STAT-6. IL13 initially binds IL-13Rα1 with low affinity and triggers association of IL4Rα, generating a high affinity heterodimeric receptor IL13R and eliciting downstream signals. IL13 also binds IL-13Rα2 with high affinity, which plays a role in a negative feedback system of IL13 signaling. IL13 is an important mediator of allergic inflammation and disease.