Interleukin-21
- OMIM: 605 384
- UniProt: Q9HBE4
Interleukin-21 (IL -21) is an interleukin that is encoded in humans by the IL21 gene.
Interleukin-21 is a cytokine with important regulatory effects on cells of the immune system, including natural killer cells (NK - cells) and cytotoxic T- cells infected with viruses or destroy cancer cells. This cytokine induces cell division and growth in its target cells.
Gene
The human IL -21 gene is about 8.43 kb in size and linked to chromosome 4 and 180 kb of the IL -2 gene. The mRNA product is 616 nucleotides long.
Distribution in tissues and cells
IL-21 is found in activated human CD4 T- cells but not in most other tissues. In addition, the IL -21 expression in different T- helper cells (eg Th17, T follicular cells ) is upregulated. Continued IL-21 in natural killer T (NK - T cells) is formed and regulates the function.
Interleukin-21 is also formed by cancer cells of Hodgkin lymphoma (HL). This observation could explain a large part of the behavior of classical Hodgkin 's lymphoma, including clusters of other immune cells to HL cells in cell cultures. IL -21 is thus in focus in the research of potential treatment approaches, or at least the development of a test for HL.
Clinical Significance
Allergies
IL- 21R - knockout mice show increased levels of IgE and IgG1 lower than wild-type mice, after they were exposed to the antigen. The IgE levels decreased after injection of IL -21. This is significant for the role in controlling allergic reactions plays IL -21, and because of the role of IgE in type 1 hypersensitivity reactions. IL- 21 therapy, attempts have been made to reduce allergic reactions. It could be shown that this pro-inflammatory cytokines produced by T cells, could be reduced, and suffering in to allergic rhinitis ( allergic rhinitis ) mice were also IgE levels are lowered. A study in mice with peanut allergy showed that systemic treatment effectively counteracted by IL -21 of the allergic reaction. This has great importance for the pharmacological development of IL -21- based drugs against local and systemic allergies.
Immunotherapy for cancer
IL- 21 was for clinical Phase 1 trials in patients with metastatic melanoma (MM) and renal cell carcinoma ( renal cell carcinoma, RCC) enabled. It was for the authorities towards presented with only flu-like side effects than secure enough. Dose - limiting toxicity was determined by low numbers of lymphocytes, neutrophils and platelets as well as on the basis of liver function tests. According to the criteria for treatment effects in solid tumors ( Response Evaluation Criteria in Solid tumor RECIST ) showed 2 of 47 MM patients and 4 of 19 RCC patients complete or partial effects. Further increases were of perforin, granzyme B, IFN- γ and CXCR3 mRNA detected in peripheral NK cells and CD8 T cells. This suggests that IL -21 to CD8 effector functions, and thereby results in promoting an anti -tumor response. With IL -21 were then performed to Clinical Phase 2 trials where it was administered alone or in combination with drugs such as sorafenib and rituximab.
Virus infections
IL-21 may be a critical factor in the control of persistent virus infections. IL-21 (or IL- 21R - ) knockout mice with the virus of chronic lymphocytic Choriomenginitis (LCM virus, LCMV ) were infected, this could not get rid of in contrast to wild-type mice. In addition, these knockout mice with defective IL -21 signaling pathway showed far more dramatic distributions of LCMV- specifischen, cytotoxic T cells, suggesting that CD4 helper T cells produced IL -21 necessary for sustained CD8 effector T cells is. Thus, it is likely that IL-21 is involved in the mechanism, orchestrate the CD4 T-helper cells, the immune system response to viral infections.
Of HIV -infected patients, it was reported that IL -21 enhanced the HIV - specific cytotoxic response of T - cells. and NK cell functions. It has also been shown that HIV-specific CD4 T - cells of long -term stability (rare cases where the AIDS disease is not formed, although they are not treated ) are able to significantly more IL -21 production than the majority of people. Moreover, in the long term a stable IL -21 -producing, virus-specific CD8 T cells were found more frequently. These data and the fact that IL-21 stimulated NK cells or CD8 were able to show the replication of HIV virus in vitro to prevent that this cytokine may possibly be used for anti-HIV therapeutic agents.