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22-441: (Redirected from IL21 ) IL-21 or IL 21 can refer to: Interleukin 21 Illinois's 21st congressional district , an obsolete district Illinois Route 21 [REDACTED] Topics referred to by the same term This disambiguation page lists articles associated with the same title formed as a letter–number combination. If an internal link led you here, you may wish to change

44-535: A heavily biased, semi-invariant T-cell receptor and NK cell markers. NKT cells are a subset of T cells that coexpress an αβ T-cell receptor, but also express a variety of molecular markers that are typically associated with NK cells, such as NK1.1 . The best-known NKT cells differ from conventional αβ T cells in that their T-cell receptors are far more limited in diversity ('invariant' or 'type 1' NKT). They and other CD1d-restricted T cells ('type 2' NKT) recognize lipids and glycolipids presented by CD1d molecules,

66-621: A member of the CD1 family of antigen-presenting molecules, rather than peptide - major histocompatibility complexes (MHCs). As such, NKT cells are important in recognizing glycolipids from organisms such as Mycobacterium , which causes tuberculosis . NKT cells include both NK1.1 and NK1.1 , as well as CD4 , CD4 , CD8 and CD8 cells. Natural killer T cells can share other features with NK cells, as well, such as CD16 and CD56 expression and granzyme production. Invariant natural killer T (iNKT) cells express high levels of and are dependent on

88-460: A non-polymorphic major histocompatibility complex class I-like antigen presenting molecule. These cells are conserved between humans and mice. The highly conserved TCR is made of Va24-Ja18 paired with Vb11 in humans, which is specific for glycolipid antigens. The best known antigen of iNKT cells is alpha-galactosylceramide (αGalCer), which is a synthetic form of a chemical purified from the deep sea sponge Agelas mauritianus. iNKT cells develop in

110-518: A pathway for NKT cells to fight against infections and enhance the humoral immunity. The NKT cells provide support and help to B cells which act as a microbial defense and aid in targeting for B-cell vaccines. NKT cells seem to be essential for several aspects of immunity because their dysfunction or deficiency has been shown to lead to the development of autoimmune diseases such as diabetes , autoinflammatory diseases such as atherosclerosis , and cancers . NKT cells have recently been implicated in

132-770: A test for HL. The IL-21 receptor ( IL-21R ) is expressed on the surface of T, B and NK cells. IL-21r is similar in structure to the receptors for other type I cytokines like IL-2R or IL-15 and requires dimerization with the common gamma chain (γc) in order to bind IL-21. When bound to IL-21, the IL-21 receptor acts through the Jak/STAT pathway, utilizing Jak1 and Jak3 and a STAT3 homodimer to activate its target genes. It has been shown that IL-21R knock-out mice express higher levels of IgE and lower levels of IgG1 than normal mice after antigen exposure. IgE levels decreased after mice were injected with IL-21. This has implications for

154-501: Is a protein that in humans is encoded by the IL21 gene . Interleukin-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. The human IL-21 gene is about 8.43kb, mapped to chromosome 4 and 180kb from IL-2 gene, and

176-415: Is in development for multiple inflammatory conditions ( Clinicaltrials.gov entries ). Natural Killer T cell The term "NK T cells" was first used in mice to define a subset of T cells that expressed the natural killer (NK) cell-associated marker NK1.1 (CD161). It is now generally accepted that the term "NKT cells" refers to CD1d-restricted T cells , present in mice and humans, some of which coexpress

198-608: Is required for sustained CD8+ T cell effector activity and then, for maintaining immunity to resolve persistent viral infection. Thus, IL-21 may contribute to the mechanism by which CD4+ T helper cells orchestrate the immune system response to viral infections. In HIV infected subjects, IL-21 has been reported to critically improve the HIV-specific cytotoxic T cell responses and NK cell functions. It has also been shown that HIV-specific CD4 T cells from “ HIV controllers ” (rare individuals who don’t progress to AIDS by controlling

220-661: The Response Evaluation Criteria in Solid Tumors ( RECIST ) response scale, 2 out of 47 MM patients and 4 out of 19 RCC patients showed complete and partial responses, respectively. In addition, there was an increase of perforin , granzyme B , IFN-γ , and CXCR3 mRNA in peripheral NK cells and CD8 T cells . This suggested that IL-21 enhances the CD8 effector functions thus leading to anti-tumor response. IL-21 proceeded to Phase 2 clinical trials where it

242-415: The function of these cells. Interleukin-21 is also produced by Hodgkin's lymphoma (HL) cancer cells (which is surprising because IL-21 was thought to be produced only in T cells ). This observation may explain a great deal of the behavior of classical Hodgkin's lymphoma including clusters of other immune cells gathered around HL cells in cultures. Targeting IL-21 may be a potential treatment or possibly

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264-814: The immune system develops. They are known to play a role in chronic inflammatory diseases like autoimmune disease, asthma and metabolic syndrome. In human autoimmune diseases, their numbers are decreased in peripheral blood. It is not clear whether this is a cause or effect of the disease. Absence of microbe exposure in early development led to increased iNKT cells and immune morbidity in a mouse model. Upon activation, NKT cells are able to produce large quantities of interferon gamma , IL-4 , and granulocyte-macrophage colony-stimulating factor , as well as multiple other cytokines and chemokines (such as IL-2 , IL-13 , IL-17 , IL-21 , and TNF-alpha ). NKT cells recognize protected microbial lipid agents which are presented by CD1d-expressing antigen presenting cells. This serves as

286-651: The link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=IL-21&oldid=1108839157 " Category : Letter–number combination disambiguation pages Hidden categories: Short description is different from Wikidata All article disambiguation pages All disambiguation pages Interleukin 21 2OQP , 3TGX 59067 60505 ENSG00000138684 ENSMUSG00000027718 Q9HBE4 Q9ES17 NM_021803 NM_001207006 NM_021782 NM_001291041 NP_001193935 NP_068575 NP_001277970 NP_068554 Interleukin 21 ( IL-21 )

308-473: The mRNA product is 616 nucleotides long. IL-21 is expressed in activated human CD4 T cells but not in most other tissues. In addition, IL-21 expression is up-regulated in T h 2 and T h 17 subsets of T helper cells , as well as T follicular cells . In fact, it was shown that IL-21 can be used to identify peripheral T follicular helper cells. Furthermore, IL-21 is expressed in NK T cells regulating

330-540: The presence of IL-21 led to a stable, 'helper-independent' phenotype. IL-21 is also noted to have anti-tumour effects through continued and increased CD8+ cell response to achieve enduring tumor immunity. IL-21 was approved for Phase 1 clinical trials in metastatic melanoma (MM) and renal cell carcinoma (RCC) patients. It was shown to be safe for administration with flu-like symptoms as side effects. Dose-limiting toxicities included low lymphocyte, neutrophil , and thrombocyte count as well as hepatotoxicity. According to

352-457: The role of IL-21 in controlling allergic responses because of the role of IgE in hypersensitivity type 1 responses. IL-21 has been tried as therapy for alleviating allergic responses. It was shown to be successful in decreasing pro-inflammatory cytokines produced by T cells in addition to decreasing IgE levels in a mouse model for rhinitis (nasal passage inflammation). A study using mice with peanut allergies showed that systemic treatment of IL-21

374-679: The thymus, and distribute to the periphery. They are most commonly found in the liver, but are also found in the thymus, spleen, peripheral blood, bone marrow and fat tissue. In comparison to mice, humans have fewer iNKT cells and have a wide variation in the amount of circulating iNKT cells. Currently, there are five major distinct iNKT cell subsets. These subset cells produce a different set of cytokines once activated. The subtypes iNKT1, iNKT2 and iNKT17 mirror Th Cell subsets in cytokine production. In addition there are subtypes specialized in T follicular helper -like function and IL-10 dependent regulatory functions. Once activated iNKT cells can impact

396-745: The transcriptional regulator promyelocytic leukemia zinc finger for their development. Classification of natural killer T cells into three groups has been proposed: The best-known subset of CD1d-dependent NKT cells expresses an invariant T-cell receptor (TCR) α chain. These are referred to as type I or invariant NKT cells (iNKT) cells. They are notable for their ability to respond rapidly to danger signals and pro-inflammatory cytokines. Once activated, they engage in effector functions, like NK transactivation, T cell activation and differentiation, B cell activation, dendritic cell activation and cross-presentation activity, and macrophage activation. iNKT cells recognize lipid antigens presented by CD1d ,

418-413: The type and strength of an immune response. They engage in cross talk with other immune cells, like dendritic cells , neutrophils and lymphocytes . Activation occurs by engagement with their invariant TCR. iNKT cells can also be indirectly activated through cytokine signaling. While iNKT cells are not very numerous, their unique properties makes them an important regulatory cell that can influence how

440-490: The virus replication without treatment) are able to produce significantly more IL-21 than those of progressors. In addition, IL-21 producing virus specific CD8 T cells were also preferentially found in HIV controllers. These data and the fact that IL-21 stimulated CD8 or NK cells are able to inhibit HIV viral replication in vitro , show that this cytokine could potentially be useful for anti-HIV therapeutics. An antibody to IL-21

462-488: Was administered alone or coupled with drugs as sorafinib and rituximab . IL-21 may be a critical factor in the control of persistent viral infections. IL-21 (or IL-21R) knock-out mice infected with chronic LCMV (lymphocytic choriomeningitis virus) were not able to overcome chronic infection compared to normal mice. Besides, these mice with impaired IL-21 signaling had more dramatic exhaustion of LCMV-specific CD8+ T cells , suggesting that IL-21 produced by CD4+ T cells

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484-513: Was an effective means of mitigating the allergic response. This has strong implications for the pharmacological development of IL-21 for controlling both localized and systemic allergies. A role for IL-21 in modulating the differentiation programming of human T cells was first reported by Li et al., where it was shown to enrich for a population of central memory-type CTL with a unique CD28+ CD127hi CD45RO+ phenotype with IL-2 producing capacity. Tumor-reactive antigen-specific CTL generated by priming in

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