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Hub AI
Interleukin 23 AI simulator
(@Interleukin 23_simulator)
Hub AI
Interleukin 23 AI simulator
(@Interleukin 23_simulator)
Interleukin 23
Interleukin 23 (IL-23) is a heterodimeric cytokine composed of an IL-12B (IL-12p40) subunit (which is shared with IL-12) and an IL-23A (IL-23p19) subunit. IL-23 is part of the IL-12 family of cytokines. The functional receptor for IL-23 (the IL-23 receptor) consists of a heterodimer between IL-12Rβ1 and IL-23R.
IL-23 was discovered in the year 2000 by Robert Kastelein and colleagues at the DNAX research institute using a combination of computational, biochemical and cellular immunology approaches.
IL-23 is an inflammatory cytokine. It has been shown to be a key cytokine for T helper type 17 cell (Th17 cell) maintenance and expansion. Polarisation to a Th17 phenotype is triggered by IL-6 and TGF-β, which activate the Th17 transcription factor RORγt. IL-23 stabilises RORγt and thus enables Th17 cells to release their effector cytokines, such as IL-17, IL-21, IL-22 and GM-CSF, which mediate protection against extracellular fungi and bacteria and participate in barrier immunity. Effects similar to those IL-23 has on Th17 cells were described for type 3 innate lymphoid cells, which actively secrete Th17 cytokines upon IL-23 stimulation. Natural killer cells also express the IL-23 receptor. They respond with increased interferon-γ secretion and enhanced antibody-dependent cellular cytotoxicity. IL-23 also induces proliferation of CD4 memory T cells (but not naïve T cells). Besides its proinflammatory effects, IL-23 promotes angiogenesis.
IL-23 is mainly secreted by activated dendritic cells, macrophages or monocytes. Innate lymphoid cells and γδ T cells also produce IL-23. B cells produce IL-23 through B cell antigen receptor signaling. Secretion is stimulated by an antigen stimulus recognised by a pattern recognition receptor. IL-23 imbalance and increase is associated with autoimmune diseases and cancer. It is thus a target for therapeutic research. IL-23 expression by dendritic cells is further induced by thymic stromal lymphopoietin, a proallergic cytokine expressed by keratinocytes that is elevated in psoriatic lesions. In the pathogenesis of psoriasis, dermal dendritic cells are stimulated to release IL-23 by nociceptive neurons. IL-23 is also elevated during bacterial meningitis, leading to epithelial dysregulation and inflammation.
Mycobacterium avium subspecies paratuberculosis-stimulated monocyte-derived macrophages are one of the contributors of IL-23, and thus cattle with Johne's disease have elevated IL-23.
Prior to the discovery of IL-23, IL-12 had been proposed to represent a key mediator of inflammation in mouse models of inflammation. However, many studies aimed at assessing the role of IL-12 by pharmacological blockade had targeted IL-12B, and were therefore not as specific as thought. Studies which blocked the function of IL-12A did not produce the same results as those targeting IL-12B, as would have been expected if both subunits formed part of IL-12 only.
The discovery of an additional potential binding partner for IL-12B led to a reassessment of this role for IL-12. Studies in experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis, showed that IL-23 was responsible for the inflammation observed, not IL-12 as previously thought. Subsequently, IL-23 was shown to facilitate development of inflammation in numerous other models of immune pathology where IL-12 had previously been implicated, including models of arthritis, intestinal inflammation, and psoriasis. Low concentrations of IL-23 support lung tumor growth whereas high concentrations inhibit proliferation of lung cancer cells. IL-23 and IL-23R were identified in serum from patients with non-small-cell lung cancer and have been proposed as prognostic serum markers. IL-23 can also promote progression of cardiovascular diseases such as atherosclerosis, hypertension, aortic dissection, cardiac hypertrophy, myocardial infarction and acute cardiac injury[citation needed]. In brain, IL-23 is able to activate γδ T cells to increase their expression of IL-17, which contributes to the inflammatory response and thus plays a key role in secondary brain injury after spontaneous intracerebral hemorrhage.
IL-23 is one of the therapeutic targets to treat the inflammatory diseases. Blocking IL-23 can slow clinical manifestation of psoriasis, indirectly affecting Th17 immune response and production of IL-17. Ustekinumab, a monoclonal antibody directed against this cytokine, is used to treat certain autoimmune conditions. Guselkumab is another monoclonal antibody against IL-23. Ixekizumab, an IL-17A antagonist, has been reported to have faster onset of action in treatment of psoriasis than tildrakizumab or risankizumab, which are inhibitors of the p19 subunit of IL-23. However, guselkumab and risankizumab has been shown to have the best treatment results for psoriasis. Adnectin-2 binds to IL-23 and competes with IL-23–IL-23R binding.
Interleukin 23
Interleukin 23 (IL-23) is a heterodimeric cytokine composed of an IL-12B (IL-12p40) subunit (which is shared with IL-12) and an IL-23A (IL-23p19) subunit. IL-23 is part of the IL-12 family of cytokines. The functional receptor for IL-23 (the IL-23 receptor) consists of a heterodimer between IL-12Rβ1 and IL-23R.
IL-23 was discovered in the year 2000 by Robert Kastelein and colleagues at the DNAX research institute using a combination of computational, biochemical and cellular immunology approaches.
IL-23 is an inflammatory cytokine. It has been shown to be a key cytokine for T helper type 17 cell (Th17 cell) maintenance and expansion. Polarisation to a Th17 phenotype is triggered by IL-6 and TGF-β, which activate the Th17 transcription factor RORγt. IL-23 stabilises RORγt and thus enables Th17 cells to release their effector cytokines, such as IL-17, IL-21, IL-22 and GM-CSF, which mediate protection against extracellular fungi and bacteria and participate in barrier immunity. Effects similar to those IL-23 has on Th17 cells were described for type 3 innate lymphoid cells, which actively secrete Th17 cytokines upon IL-23 stimulation. Natural killer cells also express the IL-23 receptor. They respond with increased interferon-γ secretion and enhanced antibody-dependent cellular cytotoxicity. IL-23 also induces proliferation of CD4 memory T cells (but not naïve T cells). Besides its proinflammatory effects, IL-23 promotes angiogenesis.
IL-23 is mainly secreted by activated dendritic cells, macrophages or monocytes. Innate lymphoid cells and γδ T cells also produce IL-23. B cells produce IL-23 through B cell antigen receptor signaling. Secretion is stimulated by an antigen stimulus recognised by a pattern recognition receptor. IL-23 imbalance and increase is associated with autoimmune diseases and cancer. It is thus a target for therapeutic research. IL-23 expression by dendritic cells is further induced by thymic stromal lymphopoietin, a proallergic cytokine expressed by keratinocytes that is elevated in psoriatic lesions. In the pathogenesis of psoriasis, dermal dendritic cells are stimulated to release IL-23 by nociceptive neurons. IL-23 is also elevated during bacterial meningitis, leading to epithelial dysregulation and inflammation.
Mycobacterium avium subspecies paratuberculosis-stimulated monocyte-derived macrophages are one of the contributors of IL-23, and thus cattle with Johne's disease have elevated IL-23.
Prior to the discovery of IL-23, IL-12 had been proposed to represent a key mediator of inflammation in mouse models of inflammation. However, many studies aimed at assessing the role of IL-12 by pharmacological blockade had targeted IL-12B, and were therefore not as specific as thought. Studies which blocked the function of IL-12A did not produce the same results as those targeting IL-12B, as would have been expected if both subunits formed part of IL-12 only.
The discovery of an additional potential binding partner for IL-12B led to a reassessment of this role for IL-12. Studies in experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis, showed that IL-23 was responsible for the inflammation observed, not IL-12 as previously thought. Subsequently, IL-23 was shown to facilitate development of inflammation in numerous other models of immune pathology where IL-12 had previously been implicated, including models of arthritis, intestinal inflammation, and psoriasis. Low concentrations of IL-23 support lung tumor growth whereas high concentrations inhibit proliferation of lung cancer cells. IL-23 and IL-23R were identified in serum from patients with non-small-cell lung cancer and have been proposed as prognostic serum markers. IL-23 can also promote progression of cardiovascular diseases such as atherosclerosis, hypertension, aortic dissection, cardiac hypertrophy, myocardial infarction and acute cardiac injury[citation needed]. In brain, IL-23 is able to activate γδ T cells to increase their expression of IL-17, which contributes to the inflammatory response and thus plays a key role in secondary brain injury after spontaneous intracerebral hemorrhage.
IL-23 is one of the therapeutic targets to treat the inflammatory diseases. Blocking IL-23 can slow clinical manifestation of psoriasis, indirectly affecting Th17 immune response and production of IL-17. Ustekinumab, a monoclonal antibody directed against this cytokine, is used to treat certain autoimmune conditions. Guselkumab is another monoclonal antibody against IL-23. Ixekizumab, an IL-17A antagonist, has been reported to have faster onset of action in treatment of psoriasis than tildrakizumab or risankizumab, which are inhibitors of the p19 subunit of IL-23. However, guselkumab and risankizumab has been shown to have the best treatment results for psoriasis. Adnectin-2 binds to IL-23 and competes with IL-23–IL-23R binding.
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