Misplaced Pages

#376623

26-471: IL-23 or IL 23 can refer to: Interleukin 23 , a protein Illinois's 23rd congressional district , an obsolete district Illinois Route 23 [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

52-539: A high affinity for antigens. TSLP may play an important role in the formation of GCs, as the depletion of TSPLR in CD 4 T cells prevented their formation in mice, as well as the generation of IgG1 . TSLP signals through a heterodimeric receptor complex composed of the TSLP receptor (TSLPR) and the IL-7Rα chain. Upon binding, Janus kinase (JAK)1 and 2 are activated, leading to

78-423: 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

104-435: A novel vaccine adjuvant and anti-cancer immunotherapy due to its broad and potent alarmin functionality, as is evidenced by numerous animal studies. Germinal centres (GCs) are microstructures that form in secondary lymphoid organs during immune responses. GCs are the sites of the clonal expansion of B lymphocytes and the affinity maturation of their antibodies , thus allowing the immune system to generate antibodies with

130-947: 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 . In brain, IL-23

156-467: A similarly acting alarmin, TSLP is usually not constitutively expressed and must be upregulated by transcription factors such as nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) or activator protein (AP)1 following insult. Local dendritic cells (DCs) are among the most important targets of TSPL, as they, among other antigen presenting cells (APCs) , allow the immune system to mount adaptive responses . TSLP signalling grants DCs

182-436: 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 ,

208-601: Is an interleukin (IL)-2 -like cytokine , alarmin , and growth factor involved in numerous physiological and pathological processes, primarily those of the immune system . It shares a common ancestor with IL-7 . Originally appreciated for its role in immune cell proliferation and development, and then for its pivotal role in type 2 immune responses , TSLP is now known to be involved in other types of immune responses , autoimmune disease , and certain cancers . TSLP production has been observed in numerous species, including humans and mice . In humans, TSLP

234-593: Is encoded by the TSLP gene . Alternative splicing of TSLP results in two transcript variants , a long form (lfTSLP, or just TSLP ) consisting of 159 amino acid residues , and a short form (sfTSLP) consisting of 63 amino acid residues. These variants use different initiation methionine codons and share a carboxy terminus . sfTSLP mRNA is constitutively expressed in normal human bronchial epithelial cells (NHBE), normal human lung fibroblasts (NHLF), and bronchial smooth muscle cells (BSMC). sfTSLP mRNA expression

260-668: Is not known whether sfTSLP also signals via the TSLP receptor complex . TSLP's pivotal role in initiating immune responses begins with its release by epithelial or stromal cells of the lungs , skin , or gastrointestinal tract as an alarmin following mechanical cell injury , pattern recognition receptor (PRR) and protease-activated receptor (PAR) activation, stimulation by certain cytokines, chemical irritation, or infection. When local mast cells bind an allergen , they produce TSLP indirectly by releasing tryptase in an FcεRI -dependent manner, activating PARs on epithelial cells and causing them to release TSLP. Unlike IL-33 ,

286-552: Is not significantly upregulated by inflammation . TSLP mRNA is not constitutively expressed in NHBE and has a low level of constitutive expression in NHLF and BSMC. TSLP mRNA expression is upregulated by certain Toll-like receptor (TLR) ligands such as flagellin and poly(I:C) , but not by lipopolysaccharide (LPS) or macrophage-activating lipopeptide 2 (MALP-2) . As the name suggests, TSLP

SECTION 10

#1732930143377

312-412: Is responsible for key Th17 development attributes such as RORγt expression and transcription of Th17 cytokines .   Thymic stromal lymphopoietin 4NN5 , 4NN6 , 4NN7 85480 53603 ENSG00000145777 ENSMUSG00000024379 Q969D9 Q9JIE6 NM_033035 NM_138551 NM_021367 NP_149024 NP_612561 NP_067342 Thymic stromal lymphopoietin ( TSLP )

338-399: 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

364-936: 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

390-564: 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

416-432: The activation of signal transducer and activator of transcription (STAT)5A and 5B and, to a lesser extent, STAT1 and 3 . These transcription factors upregulate pro-inflammatory cytokines such as IL-4 , 5 , 9 , and 13 . TSLP expression is linked to many disease states including asthma, inflammatory arthritis, atopic dermatitis, eczema, eosinophilic esophagitis and other allergic states. The factors inducing

442-400: The activation of TSLP release are not clearly defined. Expression of TSLP is enhanced under asthma -like conditions (aka Airway HyperResponsiveness or AHR model in the mouse), conditioning APCs in order to orient the differentiation of T cells coming into the lungs towards a TH2 profile (T helper 2 pathway). The TH2 cells then release factors promoting an inflammatory reaction following

468-499: The best treatment results for psoriasis. Adnectin-2 binds to IL-23 and competes with IL-23–IL-23R binding. The IL-23 heterodimer binds the receptor complex: the p19 subunit binds IL-23R while the p40 subunit binds IL-12RB1. Receptor binding leads to recruitment of Janus kinase 2 and Tyrosine kinase 2 kinases. Janus kinase 2 and Tyrosine kinase 2 transduce the signal and phosphorylate STAT3 and STAT4 . STATs dimerise and activate transcription of target genes in nucleus. STAT3

494-544: 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

520-762: The exact phenotype needed to prime naive CD 4 T cells into T H 2 pro-inflammatory cells, or producing type 2 cytokines , namely by upregulating OX40L , CD80 , and CD86 . TSLP-stimulated DCs that migrate into draining lymph nodes can prime CD 4 T cells into follicular helper T (T FH ) cells , which in turn can promote immunoglobulin (Ig)G and E production by resident B lymphocytes, thus initiating type 2 immune responses. T H 2 can also facilitate B cell class switching towards IgE. As mentioned, TSLP serves as an alarmin following TLR binding by certain pathogen-associated molecular patterns (PAMPs) , including viral and bacterial ones, rather than just irritation by allergens. Thus, TSLP also plays an early role in

546-401: The inhalation of house dust mite (HDM) antigens in mice who had been sensitised to HDM, an asthma -like model. Similarly, sfTSLP reduces the severity of dextran sulphate sodium (DSS) -induced colitis in mice, a model of inflammatory bowel disease (IBD) , and prevents endotoxic shock and sepsis resulting from bacterial infections . A receptor for sfTSLP has not been discovered. It

SECTION 20

#1732930143377

572-488: The initiation of type 1 and 3 immune responses to pathogens. This activity has thus far been best described in the respiratory mucosa. TSLP-activated CD 11 b DCs can promote the proliferation and long-term survival of CD 8 cytotoxic T cells, promoting the development of lasting adaptive cellular immunity. Analogously, TSLP-activated CD 11 c cells are essential for the development of IgA antibodies following pneumococcal infection. TSLP also holds considerable promise as

598-450: The link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=IL-23&oldid=801777277 " Category : Letter–number combination disambiguation pages Hidden categories: Short description is different from Wikidata All article disambiguation pages All disambiguation pages Interleukin 23 IL-23 was first described by Robert Kastelein and colleagues at

624-423: 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

650-465: The repeated contact with a specific antigen in the airways. TSLP-activated Langerhans cells of the epidermis induce the production of pro-inflammatory cytokines like TNF-alpha by T cells potentially causing atopic dermatitis . It is thought that by understanding the mechanism of TSLP production and those potential substances that block the production, one may be able to prevent or treat conditions of asthma and/or eczema. The TSLP signaling axis

676-562: Was initially discovered as a growth factor derived from the supernatant of a mouse thymic stromal cell line that was found to promote the survival and proliferation of B lymphocytes . TSLP was initially observed to have both pro-inflammatory and anti-inflammatory activity. It is now clear that this seemingly ambivalent action can actually be divided between the two transcript variants , with TSLP being pro-inflammatory and sfTSLP being anti-inflammatory. sfTSLP inhalation prevents airway epithelial barrier disruption caused by

#376623