Interleukin 23 receptor: Expression and regulation in immune cells.

The importance of IL-23 and its specific receptor, IL-23R, in the pathogenesis of several chronic inflammatory diseases has been established, but the underlying pathological mechanisms are not fully understood. This review focuses on IL-23R expression and regulation in immune cells.

Interleukin-23 receptor (IL-23R) gene polymorphisms and haplotypes associated with the risk of preeclampsia: evidence from cross-sectional and in silico studies.

PURPOSE: Pre-eclampsia is a relatively common pregnancy disorder. Serum concentrations of certain pro-inflammatory molecules and cytokines like interleukin-23 may affect the pathogenesis of pre-eclampsia. The interleukin-23 receptor (IL-23R) gene plays an important role in the progression of inflammatory and autoimmune diseases and IL-23 polymorphisms might influence the susceptibility of pre-eclampsia. The aim of the recent study was to establish the association between IL-23R gene polymorphisms and the susceptibility for developing of pre-eclampsia. METHODS: One hundred and fifty-eight pregnant patients with pre-eclampsia and 153 controls were genotyped using RFLP-PCR and AS-PCR. Also, an in silico analysis was performed to predict possible effects of these variations on IL-23R mRNA and protein structures. RESULTS: The frequency of the AG genotype of rs11209026 is related to a higher risk of pre-eclampsia. The mutant C and A allele in rs10889677 and rs11209026 SNPs, respectively, are correlated with the risk of pre-eclampsia and they are more frequent in severe late onset PE. We found higher frequency of the haplotype CG in patients with pre-eclampsia in comparison to healthy controls, as well as, the CG haplotype frequency significantly increased the risk of PE in severe, early onset, and late onset sub-groups. The results of computational analysis predicted rs11209026 and rs10889677 SNPs as functional variations, which can influence IL-23R mRNA and protein. CONCLUSIONS: The results of present study show positive association between polymorphisms in the IL-23R gene and pre-eclampsia. Therefore, the presence of IL-23R rs11209026, rs10889677 polymorphism might be markers for the genetic susceptibility to pre-eclampsia.

atRA Attenuates High Salt-Driven EAE Mainly Through Suppressing Th17-Like Regulatory T Cell Response Mediated by the Inhibition of IL-23R Signaling Pathway.

High salt diet (HSD) is implicated in numerous disorders, which boosts Th17 cell development and weakens immunosuppressive function of regulatory T cells (Treg cells) Treg cells, leading to the exacerbation of EAE. However, little is known regarding the harness of excessive proinflammatory responses evoked by HSD. Here we show that atRA, a key vitamin A metabolite with multifaceted immunoregulatory properties has the potential in inhibiting the proinflammatory reaction of high salt. Treatment with atRA in vivo elicited the Treg generation in cervical and axillary lymph nodes (CALs), and in CNS of experimental autoimmune encephalomyelitis (EAE). Meanwhile, the proportion of Th17-like Treg cells (RORγt-positive or GM-CSF-positive Treg cells) decreased in CALs. atRA also inhibited IL-17A expression in CD4+ effector T cells. In-vitro mechanistic studies showed that atRA inhibit IL-23R but not SGK1 expression in Treg cells and this results in maintained immunosuppressive function of Treg cells even in the presence of IL-6 and high salt. Furthermore, treatment of EAE with anti-IL-23R mAb attenuated HSD-provoked EAE progress. This was associated with a reduction in the number of CNS-infiltrating Th17 cells and an increase of CAL-Treg cells. Mechanically, treatment with atRA significantly promoted LP-CD103+CD11c+ dendritic cells, a subgroup of cells most closely involved in endogenous retinoic acid metabolism, and enhanced intestinal Aldh1a1 and Rdh10 expression from HSD-fed EAE mice. Interestingly, anti-IL-23R mAb administration also reduced IL-23R expression in Treg cells, along with the increased proportion of LP-CD103+CD11c+ dendritic cells and Rdh10 mRNA expression. In conclusion, administration of atRA might be a way to combat the proinflammatory effects of HSD. Meanwhile, systematic inhibition of IL-23R also had a moderate therapeutic potential in inhibiting inflammatory effects of high salt, which may serve as a basis for the identification of novel therapeutic strategies against HSD-driven autoimmune disorders.

IL23R as an indicator of immune infiltration and poor prognosis in intrahepatic cholangiocarcinoma: a bioinformatics analysis.

Background: Although the incidence of intrahepatic cholangiocarcinoma (CHOL) is low, the prognosis is very poor. The expression level of interleukin 23 receptor (IL23R) is linked to the occurrence and development of cancers. This study aimed to identify the role of IL23R in CHOL using bioinformatics tools and experimental validation. Methods: Circular RNA (circRNA), microRNA (miRNA), and messenger RNA (mRNA) datasets were obtained from the Gene Expression Omnibus (GEO) database, and R software was used for data analysis and visualization. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to conduct functional enrichment analysis, which was verified with gene set enrichment analysis software. Clinical data were obtained from The Cancer Genome Atlas (TCGA), and survival analyses were performed using the DriverDBv3 database and the Gene Expression Profiling Interactive Analysis website. The TIMER2.0 database provided us for immune cell infiltration analysis results of IL23R. Real-time quantitative polymerase chain reaction (RT-qPCR) was used for IL23R expression verification. Results: Differentially expressed (DE) mRNAs were enriched in phosphoinositide 3-kinase-serine/threonine kinase signaling pathway, immune-related tumor microenvironment (TME), and amino acid metabolism, etc. In addition, expression of IL23R was associated with immune infiltration-related cells. Furthermore, a circRNA-miRNA-IL23R network and a IL23R protein-protein interaction network were established. Most importantly, IL23R, as a prognostic gene, was found to have a low expression in CHOL. Conclusions: A circRNA-miRNA-IL23R network was identified, and it was found that IL23R may be a prognostic and immune-related biomarker in CHOL, which is worthy of further exploration.

NLRP3 inflammasome activates interleukin-23/interleukin-17 axis during ischaemia-reperfusion injury in cerebral ischaemia in mice.

AIMS: NLRP3 inflammasome has been reported associated with some inflammatory and autoimmune diseases. We previously researches showed that interleukin-23 (IL-23) and interleukin-17 (IL-17) aggravates the ischaemic injury of the brain tissue. However, it is poorly understood whether the NLPR3 inflammasome was involved in regulating and activating the IL-23/IL-17 axis in ischaemic stroke. We aimed to delineate whether the NLRP3 inflammasome signalling provokes the IL-23/IL-17 axis and interleukin-23 receptor (IL-23R) inducing the ischaemia-reperfusion injury of the brain in mice. MAIN METHODS: The male C57/BL6 mice with experimental transient middle cerebral artery occlusion (tMCAO) were established for cerebral ischaemia-reperfusion injury. MCC950 was utilized as a selective NLRP3 inflammasome inhibitor. NLRP3 inflammasome associated protein, IL-23/IL-17 and IL-23R were detected to investigate their changes in the brain tissue after tMCAO. KEY FINDINGS: MCC950 inhibited the NLRP3 inflammasome, which alleviated the neurological ischaemia-reperfusion injury. Inhibition the NLRP3 inflammasome signalling by treatment with MCC950 decreased the activation of IL-23/IL-17 axis and the expression of IL-23R. SIGNIFICANCE: The NLRP3 inflammasome facilitated the injury effect of the IL-23/IL-17 axis, which contributed to the cerebral ischaemia-reperfusion injury. This process was associated with IL-23R. Furthermore, this indicated that the NLRP3 inflammasome, as an important therapeutic target for ischaemic stroke, involves multiple mechanisms in ischaemia-reperfusion injury, and MCC950 is a promising way for clinical treatment.