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Facts about Interleukin-4.
It induces the expression of class II MHC molecules on resting B-cells. It enhances both secretion and cell surface expression of IgE and IgG1.
Human | |
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Gene Name: | IL4 |
Uniprot: | P05112 |
Entrez: | 3565 |
Belongs to: |
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IL-4/IL-13 family |
B cell growth factor 1; BCDF; B-cell stimulatory factor 1; BCGF1; BCGF-1; binetrakin; BSF1; BSF-1; IL4; IL-4; IL-4B_cell stimulatory factor 1; IL4E12; interleukin 4; interleukin-4; Lymphocyte stimulatory factor 1; MGC79402; pitrakinra
Mass (kDA):
17.492 kDA
Human | |
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Location: | 5q31.1 |
Sequence: | 5; NC_000005.10 (132673986..132682678) |
Secreted.
The marker IL4 is a crucial regulator of both the humoral and adaptive immune systems. It is believed that it inhibits the growth of tumors by attracting angiogenesis inhibitors and eosinophils. It is also known to play a role in control of GBM-xenografts. Because of this, it has become a valuable instrument to treat immunological diseases.
Interleukin-4 (IL-4) is an extremely active cytokine that regulates several aspects of the immune system. In addition to its antagonistic action toward IFN-g, IL-4 is found in a variety of cells and plays a vital role in the growth and differentiation of T helper T cells as well as the establishment of humoral immune. IL-4 promotes the differentiation of T cells into Th2 cells and B cells to respond to extracellular pathogens. It also promotes the growth of B cells. In addition to direct effects upon humoral immunity, IL-4 regulates the isotype switch in murine B cells. It stimulates differentiation of T cells into TH2 cells and Th2 cells, and blocks the proliferation of Th2 cells.
Cytokines play an essential role in the immune response. They control the intensity and duration of the immune response. They also regulate the differentiation and proliferation of different cells, and influence the secretion of antibodies. They can activate mature eosinophils , and stimulate B cells. Cytokines that bind to target cells can trigger the production and expression of cytokine receptors.
IL-4 binds with the IL-4Ra receptors of activated B and T cells. It also binds to receptors on macrophages, mast cells and other cells. The effects of the immune system are greater when IL-4 is found in greater amounts. It is important to know that interleukin-4 binds to receptors on activated T and B cells, as well as on mast cells.
IL-4 inhibits proinflammatory chemokines secretion. It also blocks the production of reactive oxygen and nitrogen intermediates. It also has negative feedback effects on the Th2 immune system. While IL-4 has a pleiotropic effect in the early encounter between T-cells and APC in lymphoid tissue, it is unlikely to be as important.
The IL-10 protein is an acid-sensitive 18.5-kD protein in the super family of cytokine. It functions as a negative regulator, suppressing IFN-y production and limiting dendritic cell proliferative capacity. IL-10 is a key regulator of adaptive and humoral immunity. Although it's not completely understood how IL-10 influences the regulation of innate and adaptive immunity, it plays an important part in the regulation of immune responses.
Inflammation is frequently caused by tumours and IL4 is a key player in this process. It promotes angiogenesis and is part of the inflammatory response. IL4 can also be utilized to control tumors by either encouraging eosinophils to be recruited or by inhibiting tumor angiogenesis. IL4 is produced by a variety of cells in the tumor environment, including macrophages and neutrophils as well as T cells.
It is not clear what role IL4 plays in the development of tumors and their advancement. In one clinical trial CAR-NKT cells were detected in tumor sites, and one patient had a complete remission of bone metastasis. In another trial, CARNKT cells were observed to improve survival after immunotherapy, resulting in a complete remission of the tumor.
IL4 plays a dual role in asthma. In atopic asthmatics it stimulates fibroblasts, and mucus-producing cells. It also triggers airway eosinophils to form. The primary eosinophil, IL-5, is the main cytokine, is essential for the formation of eosinophils. IL-13 and IL-4 are both produced at increased levels in asthmatic airways. Both cytokines can cause inflammation in the cells and IgE-dependent mast cell activation.
IL6 is an additional interleukin. It is believed that it can increase the eosinophil population as well the vascularization of tumours. IL6 is also a proinflammatory cytokine which encourages the growth of tumors and the progression of their growth. The IL-6 cytokine stimulates the growth of T cells and their lineage commitment to TH27 , as well as T Follicular Helper Cells. The cells of TH27 are also susceptible to adoptive cell transfer, which can trigger an increased proinflammatory response.
Both mice and humans have T cell lines that produce IL-22 that can be found in tumors forming in the nascent stage. This cytokine triggers STAT3 Phosphorylation and provides migration and proliferation signals to cancerous cells. IL-22 has similar functions in the treatment of cancer, since it assists in the transformation of malignant cells to normal tissues. It not only boosts T and NK cell activity, but also encourages stemness as well as the production of microbicidal peptides.
It is a different cytokine that is involved in tumor control. It regulates the growth of sympathetic axons as well as Eosinophils, and also regulates the extracellular matrix. It also regulates leukocyte and cell adhesion. In addition, it is crucial in maintaining the polar orientation of cells.
IL4 can be added to GBM xenografts for the purpose of triggering regression of tumors. IL4 suppresses the immune response in GBM cells. This is associated with decreased pericytes of the xenograft. However this effect isn't only restricted to GBM cells. It could also be caused by an immunotolerance condition that facilitates the anchorage of grafted cells to areas of perivascularization.
Human GBM cells were co-cultured in murine pericytes for 72 hours. The xenografts were created according to previous studies in immunocompetent mice. They were made into hanging drops and then inserted into a small craniotomy. With the help of a stereotactic instrument the grafts are injected through an 0.38-mm hole in the brain.
The biological function of IL-4 and IL-13 is not certain. The reason for this is that cytokine production can differ depending on the type of tumor and cell lines. It is essential that each patient receives the appropriate treatment for their immunotoxicity. IL-4 and IL-13 immunotoxins have shown promise in GBM treatment and have been tested in clinical trials to test this idea. Further research is needed to investigate the role of these toxins in the treatment of advanced intestinal cancers.
In GBM+Pc cultured with pericytes proliferating GBM cells are found in xenografts of immunocompetent C57Bl/6 mice. Most GBM+Pc grafts exhibited GBM tumors. Pericytes did not show up in the xenografts used to control. GBM+Pc cells resulted into immune-competent mice. Tumors were identified in three of the four grafts.
While targeting IL4 in GBM xenograft models is a challenging task, it is vital in the development of an immunotherapy that targets the protein. Its specific expression was first discovered in GBM cells nearly two decades ago, which led to its recognition as a target. This article will review the various options of drugs that treat IL4 and consider potential new strategies for treatment.
Researchers have been working on targeted treatments for GBM in recent years. One of the targets, the IL13Ra2 receptor, is a target for IL-13. Different therapies that target IL13Ra2 are available as well as fusion proteins of IL-13 with nanoparticles from bacterial toxins and oncolytic virus. A combination of IL-13 and NKT cells could also be used to inhibit GBM cell growth.
IL4 is a major regulator of immune function. It is involved in the development of various immunological conditions. It is involved in a variety of tasks, including controlling immune cell growth, secretion and hemopoiesis. It also plays crucial roles in inflammation and effector T-cell responses. It is mostly produced by activated hematopoietic hematopoietic cells such as mast cells and basophils.
In COPD, IL4 is expressed more frequently in BAL fluids than in healthy people. It is essential in the differentiation of Th2 cells from Th0 cells. It also plays a role when allergens are first sensitized. The receptor for IL4 is located on the CXCR3 protein. Once activated, IL4 promotes the production of IgE by Th2 cells.
IL4 also plays a role in tissue regeneration and repair. The expression of this cytokine rises in fibrosis of tissues and in regeneration following tissue damage. This kind of immune reaction can have both positive and negative effects. This means that therapeutic strategies that target one arm of the immune system could result in an increase in the other. IL4 is vital for tissue repair and regeneration to prevent the development of immunological disorders.
Additionally, IL4 has an important role in the pathogenesis of a variety of inflammatory diseases. In psoriasis vulgaris, IL-23 plays a major role. It causes hyperproliferative keratinocytes in the skin of patients with psoriasis. Inflammation can also contribute to bone loss. Type 2 immunity could be a factor in the development of these conditions.
While IL-4 is necessary for peripheral tolerance and controlling immune response, it could also have negative consequences. In mice, a decline in Treg function is linked to severe autoimmune diseases. It does not have a significant influence on the activation of T cells with polyclonal clones however it may affect Treg function. A study conducted in mice demonstrated that preincubation of Tregs with IL-4 enhanced their suppressive capacity. Additionally, IL-4 preserves Foxp3 expression in Tregs.
IL4 could also play a role in aging and other neurodegenerative diseases. It is crucial that IL4 is present in the brains of rats and mice but not in the blood of humans. It stimulates VCAM-1 as well as IL-8 expression, which leads to the infiltration of neutrophils. Both cytokines affect neurodegeneration.
PMID: 3016727 by Yokota T., et al. Isolation and characterization of a human interleukin cDNA clone, homologous to mouse B-cell stimulatory factor 1, that expresses B- cell- and T-cell-stimulating activities.
PMID: 2535858 by Arai N., et al. Complete nucleotide sequence of the chromosomal gene for human IL-4 and its expression.
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