Interleukin-21(IL-21) is an approximately 14 kDa cytokine which belongs to the IL-15/IL-21 family. Mature mouse IL-21 shares 66%,59%, 58%, and 88% aa sequence identity with mature canine, human, rabbit, and rat IL-21, respectively. IL-21 is produced by activated T follicular helper cells (Tfh), Th17 cells, and NKT cells. It exerts its biological effects through a heterodimeric receptor complex (IL-21 specific IL-21 R). IL-21 is a cytokine that has potent regulatory effects on cells of the immune system, including natural killer (NK) cells and cytotoxic T cells that can destroy virally infected or cancerous cells. This cytokine induces cell division/proliferation in its target cells. It is required for the migration of dendritic cells to draining lymph nodes .It co-stimulates the activation, proliferation, and survival of CD8+ T cells and NKT cells and promotes Th17 cell polarization. It blocks the generation of regulatory T cells and their suppressive effects on CD4+ T cells.
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.
Interleukin 23 (IL-23) is a heterodimeric cytokine composed of two disulfide-linked subunits, a p19 subunit that is unique to IL-23, and a p40 subunit that is shared with IL-12. The p19 subunit has homology to the p35 subunit of IL-12, as well as to other single chain cytokines such as IL-6 and IL-11. The p40 subunit is homologous to the extracellular domains of the hematopoietic cytokine receptors. Although p19 is expressed by activated macrophages, dendritic cells, T cells, and endothelial cells, only activated macrophages and dendritic cells express p40 concurrently to produce IL-23. IL-23 has biological activities that are similar to, but distinct from IL-12. Both IL-12 and IL-23 induce proliferation and IFN-gamma production by human T cells. While IL-12 acts on both naive and memory human T cells, the effects of IL-23 is restricted to memory T cells.
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 effect on cytokine production. It suppresses proinflammatory cytokine production such as IL2, IL4, IL5 and IL6 and activates suppressors of cytokine signaling such as SOCS1 and SOCS3. Apart from suppression of cytokine production, IL-27 also antagonizes the effects of some cytokines such as IL6 through direct effects on T-cells. Another important role of IL-27 is its antitumor activity as well as its antiangiogenic activity with activation of production of antiangiogenic chemokines such as IP-10/CXCL10 and MIG/CXCL9.
Interleukin 2 (IL 2), also termed T-cell growth factor, is a member of the cytokine family which includes IL-4, IL-7, IL-9, IL-15 and IL-21. Each member of this family has a four alpha helix bundle. IL-2 signals through the IL-2 receptor, a complex consisting of tree subunits, termed alpha, beta and gamma. The IL-2 R gamma is shared by cytokine receptors of all members of cytokine family. Mature mouse IL-2 shares 56% and 73% aa sequence identity with human and rat IL-2, respectively. IL-2 is produced by CD4+ T cell, CD8+ T cells, gamma δ T cells, B cells, dendritic cells and eosinophils, and plays a vital role in key function of the immune system, tolerance and immunity, primarily via its potent stimulatory activity for T cells.Thus, IL-2 may be a key cytokine in the natural suppression of autoimmunity.
Interleukin-2, also known as T-cell growth factor, TCGF, Aldesleukin and IL2, is a secreted protein which belongs to the IL-2 family. Interleukin-2 / IL-2 is produced by T-cells in response to antigenic or mitogenic stimulation, this protein is required for T-cell proliferation and other activities crucial to regulation of the immune response. Interleukin-2 / IL-2 is normally produced by the body during an immune response. Antigen binding to the T cell receptor (TCR) stimulates the secretion of Interleukin-2 / IL-2, and the expression of IL-2 receptors IL-2R. The IL-2 / IL-2R interaction then stimulates the growth, differentiation and survival of antigen-selected cytotoxic T cells via the activation of the expression of specific genes. Interleukin-2 / IL-2 can stimulate B-cells, monocytes, lymphokine-activated killer cells, natural killer cells, and glioma cells. The World Reference Standard for Interleukin-2 / IL-2 is produced by the National Institute of Biological Standards and Control in the UK. A recombinant form of Interleukin-2 / IL-2 for clinical use is manufactured by Chiron Corporation with the brand name Proleukin. It has been approved by the Food and Drug Administration (FDA) for the treatment of cancers (malignant melanoma, renal cell cancer), and is in clinical trials for the treatment of chronic viral infections, and as a booster (adjuvant) for vaccines. The use of Interleukin-2 / IL-2 in HIV therapy has been found to be ineffective.
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