Interleukin-23 (IL-23) is a cytokine composed of an IL12B (IL-12p40) subunit (that is shared with IL12) and the IL23A (IL-23p19) subunit.
The IL-23 receptor has been identified and is composed of IL-12R β1 and IL-23R.
IL-23 is mainly secreted by activated dendritic cells, macrophages or monocytes.
A key cytokine for Th17 maintenance and expansion.
Interleukins 12 and 23 are cytokines that are produced by myeloid cells that stimulate the activation of T helper lymphocytes, which in turn release, immunoactivating cytokines, such as interferon gamma and Interleukin, 17 and 22.
IL-23 acts at the top of the inflammatory pathway, activating the proliferation of pathogenic Th17 cells and subsequent production of proinflammatory cytokines, including IL-17.
Th17 are polarized by IL-6 and TGF-β which activate Th17 transcription factor RORγt.
It enables Th17 to function and release their effector cytokines such as IL-17, IL-21, IL-22 and GM-CSF which mediate protection against fungi and bacteria and participate in barrier immunity.
Lymphoid cells and NK cells actively secrete Th17 cytokines upon IL-23 stimulation, and respond with increased IFN-γ secretion and enhanced antibody-dependent cellular cytotoxicity.
IL-23 induces proliferation of CD4 memory T cells, and promotes angiogenesis.
IL-23 plays a critical role in modulating inflammatory and immune responses.
The IL-23/Th17 pathway is crucial for the pathogenic mechanisms of psoriasis.
IL-23 is considered the “master cytokine” since it acts at the top of the inflammatory pathway, activating the proliferation of pathogenic Th17 cells and subsequent production of proinflammatory cytokines, including IL-17.
IL-23 heterodimer binds the receptor complex – p19 subunit binds IL-23R while p40 subunit binds IL-12RB1 which leads to recruitment of Janus kinase 2 and Tyrosine kinase 2 kinases.
IL-23 is a heterodimer with two subunits, p19 and p40.
The p40 subunit is also shared with IL-12, a cytokine that is involved in the immune response.
Janus kinase 2 and Tyrosine kinase 2 transduce the signal and phosphorylate STAT3 and STAT4.
STAT3 is responsible for key Th17 development.
Interleukin-23 consists of a p19 subunit that associates with the IL-12p40 subunit.
It interacts with a receptor complex, which is composed of the IL-12Rβ1 subunit and an IL-23R subunit that shares homology with the IL-12β2 subunit.
Along with IL-12, IL-23 plays an important bridging role between the innate and adaptive immune responses.
The presence of neutralizing, anti–interleukin 23 is associated with severe, persistent, opportunistic infections.
It induces the production of IFN-γ from activated CD4+ T-lymphocytes but not from naïve lymphocytes.
In contrast IL-12 promotes IFN-γ production from both naïve and memory subsets.
It stimulates the proliferation of memory T-lymphocytes but not naïve T-lymphocytes, and it enhances the elaboration of IL-17 primarily from γδ T-lymphocytes.
Interleukin-17 receptors are expressed on a wide range of cell types.
IL-17 induces production of several cytokines including granulocyte colony-stimulating factor, IL-1, IL-6, IL-8, and TNF-α.
IL-17 may mediate anti-TB activity through increased phagocytosis and proinflammatory actions.
Th17 are polarized by IL-6 and TGF-β which activate Th17 transcription factor RORγt.
IL-23 stabilizes RORγt and thus enables Th17 to properly function and release their effector cytokines such as IL-17, IL-21, IL-22 and GM-CSF.
These effector cytokines mediate protection against extracellular fungi and bacteria,and participate in barrier immunity.
NK cells express IL-23 receptor, and they increase IFN-γ secretion and enhanced antibody-dependent cellular cytotoxicity.
IL-23 also induces proliferation of CD4 memory T cells.
IL-23 increase is associated with autoimmune and malignant diseases.
It facilitates development of inflammation in numerous immune pathology.
Ustekinumab, a monoclonal antibody directed against this cytokine, is used clinically to treat certain autoimmune conditions.
IL-23 heterodimer binds the receptor complex – p19 subunit binds IL-23R while p40 subunit binds IL-12RB1 which leads to recruitment of Janus kinase 2 and Tyrosine kinase 2 kinases.
Janus kinase 2 and Tyrosine kinase 2 then phosphorylate STAT3 and STAT4.
STATs dimerize and activate transcription of target genes in the nucleus.
Interleukin 23 (IL-23) is a heterodimeric cytokine belonging to the IL-6 / IL-12 family.
One of the key functions of IL-23 is its role in the activation of the Th17 pathway.
Has a critical role in both the development of autoimmune diseases as well as a protective role against infections.
IL-23 to can either hinder or aid in immunity.
It is composed of two subunits, one p40 and one p19.
The p40 subunit is identical to the one found in IL-12.
Some antibodies made for IL-12 target the p40 subunit of IL-12 and therefore can also be used against IL-23.
IL-23 has a role in chronic inflammation, a common characteristic of many autoimmune diseases.
IL-23 promotes the Th17 pathway.
The Th17 pathway is active in the pathogenesis of chronic inflammatory diseases, including psoriasis, inflammatory bowel disease, arthritis, and multiple sclerosis.
In inflammatory bowel disease, stimulation of colonic leukocytes by IL-23 induces the production of IL-17.
Blocking the IL-23 might be beneficial for the treatment of inflammatory bowel diseases.
In rheumatoid arthritis IL-23 levels are significantly higher in the peripheral blood than in normal controls.
IL-23 plays an active role in lupus nephritis.
It is elevated in psoriasis patients.
An anti-IL-23 monoclonal antibody, ustekinumab is used to treat patients with psoriasis.
The Th17 pathway and IL-23 receptor are involved in the development of Ankylosing Spondylitis (AS).
But, not all studies show that AS is not associated with IL-23R.
IL-23 levels are elevated in serum and cerebrospinal fluid in amyotrophic lateral sclerosis (ALS) patients as compared to patients with non-inflammatory neurological disorders.
IL-23 signaling regulates allergic asthma inflammation.
Its over-expression increases the airway inflammation while deficiency in IL-23 reduces airway inflammation.
IL-23 is partly responsible for cachexia and inflammation in schistosomiasis.
The suppression of IL-23 p40 in acute schistosomiasis improves both the inflammation and cachexia.
IL-23 is necessary to induce production of IL-12 in bacterial infections such as Mycobacteria and Salmonellae.
IL-23 is induced by TLR (Toll- like receptors) agonists and the production of IL-23 is necessary for IL-12 production, which is critical in providing immunity.
IL-23 is important in the clearance of streptococcus pneumoniae infection
Additionally, IL-23 is required for protection against infection with Listeria monocytogenes. IL-23 is necessary for the regulation of IL-17A and necessary for optimal liver neutrophil recruitment, which is required to eliminate the bacteria and have the host survive.17
Indeed, IL-23 has an important role in autoimmunity. IL-23 is critical for the creation and maintenance of gammadelta and double negative alphabeta T cells. These cells are important components of early, protective immune response and are regulated by IL-23.18
IL-23 has also been shown to aid in the survival from fungal infections.
With HIV infections IL-23 production increases significantly, and is coupled with a decrease in IL-12 production, which is harmful as IL-12 enhances the body’s protective response against HIV.
IL-23 to promotes tumor growth and tumor incidence.
IL-23 may block natural or cytokine induced immunity as well as promoting tumor development.
Some research that points towards IL-23 having an anti-tumor immune responses.
Dendritic cells (DC) treated with prostaglandin E(2) have a decrease of extracellular signal related kinase (ERK) activation, which is responsible for a decrease in IL-23 production.
Celecoxib and TFM-C are also capable of blocking the secretion of IL-23.
Protein phosphatase 2A (PP2A) inhibits IL-23 production in dentritic cells by suppressing the p19 subunit of IL-23.
Inhibiting the PP2A enhances IL-23 production.
IFN-gamma is a inhibitor of IL-23.
In patients with latent tuberculosis, tuberculin skin test (TST) with a positive result is associated with a decrease in IL-23 and IL-17.
IL-23 is a possible biomarkers in lupus nephritis.