Interleukin-4, also known as IL4, is a secreted protein that belongs to the IL-4 / IL-13 family. Interleukin-4 / IL4 has many biological roles, including the stimulation of activated B-cell and T-cell proliferation. It enhances both secretion and cell surface expression of IgE and IgG1. Interleukin-4 / IL4 also regulates the expression of the low-affinity Fc receptor for IgE (CD23) on both lymphocytes and monocytes. Interleukin-4 is essential for the switching of B cells to IgE antibody production and the maturation of T helper (Th) cells toward the Th2 phenotype. It participates in at least several B-cell activation processes as well as other cell types. However, studies show that double mutant (Q116D, Y119D) of the murine IL4 protein (QY), both glutamine 116 and tyrosine 119, which binds to the IL4 receptor alpha, completely inhibits in a dose-dependent manner the IL4-induced proliferation of lipopolysaccharide-stimulated murine splenic B-cells, of the murine T cell line CTLL-2, and the murine pre-B-cell line BA/F3. QY also inhibited the IL4-stimulated up-regulation of CD23 expression by lipopolysaccharide-stimulated murine splenic B-cells and abolished tyrosine phosphorylation of the transcription factor Stat6 and the tyrosine kinase Jak3 in IL4-stimulated BA/F3 cells.
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.
IL-5 is expressed in eosinophils, NK cells, TC2 CD8+ T cells, mast cells, CD45+ CD4+ T cells, gamma delta T cells and IL-1 beta activated endothelial cells. IL-5 acts as a growth and differentiation factor for both B cells and eosinophils. Relative to B cells, IL-5 appears to induce the differentiation of activated conventional B-2 cells into Ig-secreting cells. In addition, it induces the growth of B-1 progenitors as well as IgM production by B-1 cells.IL-5 appears to perform a number of functions on eosinophils. These include the down modulation of Mac-1,the upregulation of receptors for IgA and IgG,the stimulation of lipid mediator (leukotriene C4 and PAF) secretion and the induction of granule release.IL-5 also promotes the growth and differentiation of eosinophils.
Interleukin-6 (IL-6) is a pro-inflammatory cytokine that also has an important role in immunity. Mouse IL-6 appears to be directly involved in the responses that occur after infection and injury and may prove to be as important as IL-1 in regulating the acute phase response. Mouse IL-6 is reported to be produced by fibroblasts, activated T cells, activated monocytes or macrophages, and endothelial cells. It acts upon a variety of cells, including fibroblasts, myeloid progenitor cells, T cells, B cells and hepatocytes. IL-6 has a wide variety of biological functions: it plays an essential role in the final differentiation of B-cells into Ig-secreting cells, it induces myeloma and plasmacytoma growth, nerve cells differentiation in hepatocytes, and acute phase reactants.
IL7, also known as interleukin 7, is a hematopoietic growth factor that belongs to the IL-7/IL-9 family. It is secreted by stromal cells in the bone marrow and thymus. IL7 stimulates the proliferation of lymphoid progenitors. It is important for proliferation during certain stages of B-cell maturation. IL7 and the hepatocyte growth factor (HGF) form a heterodimer that functions as a pre-pro-B cell growth-stimulating factor. It is found to be a cofactor for V(D)J rearrangement of the T cell receptor beta (TCRß) during early T cell development. IL7 can be produced locally by intestinal epithelial and epithelial goblet cells and may serve as a regulatory factor for intestinal mucosal lymphocytes.
Interleukin-9 (IL-9) is a secreted protein that belongs to the IL-7/IL-9 family.Mature mouse IL-9 shares 57% and 74% amino acid sequence identity with human and rat IL-9, respectively. IL-9 supports IL-2 independent and IL-4 independent growth of helper T-cells. IL-9 stimulates cell proliferation and prevents apoptosis. It functions through the IL-9 receptor (IL-9R), which activates different signal transducer and activator (STAT) proteins and thus connects this cytokine to various biological processes. IL-9 has been identified as a candidate gene for asthma. IL-9 is a determining factor in the pathogenesis of bronchial hyperresponsiveness.
IL-2-inducible T cell kinase is a member of the protein kinase superfamily, Tyr protein kinase family and TEC subfamily. It contains 1 Btk-type zinc finger, 1 PH domain, 1 protein kinase domain, 1 SH2 domain and 1 SH3 domain. As an intracellular kinase which expressed in T-cells, IL-2-inducible T cell kinase contains both SH2 and SH3 domains which are often found in intracellular kinases. It is hought to play a role in T-cell proliferation and differentiation. It regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. IL-2-inducible T cell kinase also plays an essential role in regulation of the adaptive immune response. efects in IL-2-inducible T cell kinase are the cause of lymphoproliferative syndrome EBV-associated autosomal type 1 (LPSA1). LPSA1 is a rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus (EBV). Inadequate immune response to EBV can have a fatal outcome. Clinical features include splenomegaly, lymphadenopathy, anemia, thrombocytopenia, pancytopenia, recurrent infections. There is an increased risk for lymphoma.
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