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IL13 is an immunoregulatory cytokine produced primarily by activated Th2 cells. IL-13 is involved in several stages of B-cell maturation and differentiation. It up-regulates CD23 and MHC class II expression, and promotes IgE isotype switching of B cells. This cytokine down-regulates macrophage activity, thereby inhibits the production of pro-inflammatory cytokines and chemokines. This cytokine is found to be critical to the pathogenesis of allergen-induced asthma but operates through mechanisms independent of IgE and eosinophils. This gene, IL3, IL5, IL4, and CSF2 form a cytokine gene cluster on chromosome 5q, with this gene particularly close to IL4.

IRF5 belongs to the interferon regulatory factor (IRF) family, which is a group of transcription factors with diverse roles, including virus-mediated activation of interferon, and modulation of cell growth, differentiation, apoptosis, and immune system activity. Members of the IRF family are characterized by a conserved N-terminal DNA-binding domain containing tryptophan (W) repeats.

IL17D modulates immune responses indirectly by stimulating the production of myeloid growth factors and chemokines, as well as suppressing the proliferation of myeloid progenitors. IL17D is expressed in the skeletal muscle, heart, adipose tissue, lung, pancreas, and nervous system. Among IL-17 family members, IL17D is most closely related to IL17B, sharing 27% aa sequence identity. The treatment of endothelial cells with IL17D cytokine stimulates the production of other cytokines including IL6, IL8 and CSF2/ GM-CSF. The increased expression of IL8 induced by IL17D cytokine is NF-kappa B-dependent.

Interleukin-9 is a protein that acts as one of the regulators of hematopoiesis. IL-9 is an enhancer of cells and megakaryoblastic leukemic cells’ growth. Among this protein’s producers we can find cells like mast cells, Treg, NKT cells, Th17, Th2, ILC2, and Th9 cells in various amounts. Th9 are the primary CD4 cells (T cells) that IL-9 is produced in.

IL17 is a proinflammatory cytokine produced by activated T cells. IL-17 regulates the activities of NF-kappaB and mitogen-activated protein kinases. Interleukin-17 can stimulate the expression of IL6 and cyclooxygenase-2 (PTGS2/COX-2), as well as enhance the production of nitric oxide (NO). High levels of IL-17 are associated with several chronic inflammatory diseases including rheumatoid arthritis, psoriasis and multiple sclerosis.

Interleukin-21 isoform 1 or IL21, categorized as a T helper cytokine. IL21 is part of the regulation of immune responses, haematopoiesis and cell-mediated responses. IL21 has a key role in haematopoiesis and immune responses regulation, therefore can affect lymphocyte development. Activation of T cells leads to production of the IL21. The protein has a crucial role in the viral infections persistence.

Active IL-12 is a p70 disulphide-linked dimer composed of p35 and p40 subunits. The protein is a pleiotropic cytokine produced primarily by antigen presenting cells and has multiple effects on T lymphocytes and natural killer cells in terms of stimulating cytotoxicity, proliferation, production of other cytokines and Th1 subset differentiation.

Interleukin-21 isoform 1 or IL21, categorized as a T helper cytokine. IL21 is part of the regulation of immune responses, haematopoiesis and cell-mediated responses. IL21 takes a main part in haematopoiesis and immune responses regulation, therefore can affect lymphocyte development. Activation of T cells leads to production of the IL21 which has an important role in the viral infections persistence.

IFNs are cytokines that are widely known to induce potent anti-viral activity. IFN-a exerts a variety of other biological effects, including antitumor and immunomodulatory activities and are increasingly used clinically to treat a range of malignancies, myelodysplasias and autoimmune diseases.

Interleukin-1 receptor type 1 (IL1R1) associates with the co-receptor IL1RAP to form the high affinity interleukin-1 receptor complex, which mediates interleukin-1-dependent activation of NF-kappa-B, MAPK and other pathways. IL1R1 is a central mediator involved in numerous cytokine induced immune and inflammatory responses.

IFN-alpha is produced by macrophages and has antiviral activities. IFN stimulates the production of two enzymes: protein kinase and an oligoadenylate synthetase.

CD-90 plays a role in cell-cell or cell-ligand interactions during synaptogenesis and other events in the brain Thy-1 is the designation for a major cell surface glycoprotein characteristic to T cells,. The Thy-1 glycoproteins are constituents of thymocytes and neurons and probably are involved in cell-cell interactions. Human Thy-1 homolog maps to chromosome 11 because that is where T3D is found, in the mouse T3D and Thy-1 map to chromosome 9 along with certain other loci that are on human 11q.

CD3 has four peptide chains (gamma, delta, epsilon and zeta) that form CD3. Defects in CD3 are associated with T cell immunodeficiency CD3 complex mediates signal transduction.

Factor that is thought to be a regulator of hematopoiesis. It has been shown to enhance the growth of human mast cells and megakaryoblastic leukemic cells as well as murine helper t-cell clones. IL-9 is a glycoprotein with a molecular weight of 32-39 that is derived from T-cells, and maps to human chromosome 5.

CD28 co-stimulation is necessary for CD4 positive T-cell proliferation & survival, interleukin-2 production, and T-helper type-2 development. Human post-thymic regulatory T cells require CD28 co-stimulation to expand and maintain potent suppressive function in vivo. Apoptosis plays a key role in the age-related decline of CD28 expression and in immunosenescence.

ITGAL encodes the integrin alpha L chain. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This I-domain containing alpha integrin combines with the beta 2 chain (ITGB2) to form the integrin lymphocyte function-associated antigen-1 (LFA-1), which is expressed on all leukocytes. LFA-1 plays a central role in leukocyte intercellular adhesion through interactions with its ligands, ICAMs 1-3 (intercellular adhesion molecules 1 through 3), and also functions in lymphocyte costimulatory signaling.

Resistin, a product of the RSTN gene, is a peptide hormone belongs to the class of cysteine-rich secreted proteins (monomeric peptide contains 11 cysteine residues) referred to as the RELM family, and is also described as ADSF (Adipose Tissue-Specific Secretory Factor) or FIZZ3 (Found in Inflammatory Zone 3). Resistin may be an important link between obesity. Mouse resistin, specifically produced and secreted by adipocyte, acts on skeletal muscle myocytes, hepatocytes and adipocytes themselves so that it reduces their sensitivity. Steppan et al. have suggested that resistin suppressed the ability to stimulate glucose uptake. They have also suggested that resistin was present at elevated levels in blood of obese mice, and was down regulated by fasting and by antidiabetic drugs. Way et al., on the other hand, have found that resistin expression is severely suppressed in obesity.
Other studies have shown that mouse resistin increases during the differentiation of adipocytes, but it also seems to inhibit adipogenesis. In contrast, the human adipogenic differentiation is likely to be associated with a down regulation of resistin gene expression.

Excess adiposity is the most important risk in the development of insulin resistance and type 2 diabetes mellitus (T2DM). Adipose tissue produces several proteins (adipocytokines) such as leptin, adiponectin, resistin, tumor necrosis factor-α, and IL-6, that modulate insulin sensitivity and appear to play an important role in the pathogenesis of insulin resistance, diabetes, dyslipidemia, inflammation, and atherosclerosis. However, the mechanisms by which fat tissue induces insulin resistance and the role of adipocytokines in the pathogenesis of T2DM have not been well established. Visfatin, also known as pre-B cell colony-enhancing factor (PBEF), is a cytokine that is highly expressed in visceral fat and was originally isolated as a secreted factor that synergizes with IL-7 and stem cell factors to promote the growth of B cell precursors. Visfatin homologs have been identified in carp, invertebrate mollusks, and bacteria, as well as in vertebrates, including humans and the mouse. It h

GH is a member of the somatotropin/prolactin family of hormones which play an important role in growth control. The gene, along with four other related genes, is located at the growth hormone locus on chromosome 17 where they are interspersed in the same transcriptional orientation; an arrangement which is thought to have evolved by a series of gene duplications. The five genes share a remarkably high degree of sequence identity. Alternative splicing generates additional isoforms of each of the five growth hormones, leading to further diversity and potential for specialization. This particular family member is expressed in the pituitary but not in placental tissue as is the case for the other four genes in the growth hormone locus. Mutations in or deletions of the gene lead to growth hormone deficiency and short stature.

Interleukin 33 (IL-33) is a 32kDa proinflammatory cytokine that may also regulate gene transcription in producer cells. IL-33 is structurally related to IL-1, which induces helper T cells to produce type 2 cytokines and acts through the receptor IL1RL-1 (IL1 receptor-like-1), which is known also as ST2. Binding of IL-33 to this receptor activates NF-kappa-B and MAP kinases and induces in vitro Th2 cells to produce cytokines. In vivo, IL-33 induces expression of IL-4, IL-5, IL-13 and leads to severe pathological changes in mucosal organs and in vitro, it can be divided to N-terminal fragment of 12kDa and C-terminal fragment of 18kDa by cleavage of caspase-1.

IL20 is a cytokine structurally related to interleukin 10 (IL10). IL20 cytokine has been shown to transduce its signal through signal transducer and activator of transcription 3 (STAT3) in keratinocytes. A specific receptor for this cytokine is found to be expressed in skin and upregulated dramatically in psoriatic skin, suggesting a role for this protein in epidermal function and psoriasis.

IL-28B is a cytokine remotely related to type I IFNs and the IL-10 family. Interleukin-28B, interleukin 28A (IL28A), and interleukin 29 (IL29) are 3 closely related cytokine genes which form a cytokine gene cluster on a chromosomal region mapped to 19q13. Expression of the cytokines encoded by these 3 genes can be induced by viral infection. All 3 cytokines interact with a heterodimeric class II cytokine receptor which consists of interleukin 10 receptor, beta (IL10RB) and interleukin 28 receptor, alpha (IL28RA).

IL-17F having an accession number of Q96PD4 is a cytokine that shares sequence similarity with IL17. IL-17F is expressed by activated T cells, and has been shown to stimulate the production of several other cytokines, including IL6, IL8, and CSF2/GM_CSF. IL-17F inhibits the angiogenesis of endothelial cells and induce endothelial cells to produce IL2, TGFB1/TGFB, and monocyte chemoattractant protein-1. IL-17F induces stromal cells to produce proinflammatory and hematopoietic cytokines. Intestinal IL17F gene expression is increased in active CD.
IL-17A & IL-17F alleles influence the susceptibility to and pathophysiological features of ulcerative colitis independently. IL-17F and MIF gene polymorphisms are significantly associated with the development of functional dyspepsia.
The initiation of IL-17F/IL-17R signaling pathway requires the receptor ubiquitination by TRAF6. IL-17F induces expression of IFN-gamma-inducible protein 10 (IP-10) by activating Raf1-mitogen-activated protein kinase 1/2-extracellular-regulated kinase 1/2-p90 ribosomal S6 kinase-cyclic AMP response element-binding protein signaling pathway.