Bulk RNA-seq of interleukin-23 receptor (IL-23R) -deficient and IL-23R-sufficient colonic mouse regulatory T cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE208621 | GEO | 2023/02/17
REPOSITORIES: GEO
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Project description:Bulk RNA-seq of interleukin-23 receptor (IL-23R) -deficient and IL-23R-sufficient colonic mouse regulatory T cells
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Project description:The pro-inflammatory cytokine interleukin-23 (IL-23) has been implicated in colorectal carcinogenesis (CRC). Yet, the cell-specific contributions of IL-23 receptor (IL-23R) signaling in CRC remain unknown. One of the cell types that highly expresses IL-23R are colonic regulatory T cells (Treg cells). The aim of this study was to define the contribution of Treg cell-specific IL-23R signaling in sporadic and inflammation-associated CRC. In mice, the role of IL-23R in Treg cells in colitis-associated cancer (CAC) was investigated using azoxymethane/dextran sodium sulphate in wild-type Treg cell reporter mice (WT, Foxp3YFP-Cre), and mice harboring a Treg cell-specific deletion of IL-23 (Il23rΔTreg). Il23rΔTreg mice had increased dysplasia compared to WT mice associated with decreased tumor-infiltrating macrophages. The role of Treg cell IL-23R in sporadic CRC was examined via orthotopic injection of the syngeneic colon cancer cell line MC-38 submucosally into the colon/rectum of mice. In the sporadic cancer model, Il23rΔTreg mice had increased survival and decreased tumor size compared to WT mice. Additionally, MC-38 tumors of Il23rΔTreg mice had a higher frequency of pro-inflammatory macrophages and IL-17 producing CD4+ T cells. This data suggests that loss of IL-23R signaling in Treg cells permits IL-17 production by CD4+ T cells that in turn promotes pro-inflammatory macrophages to clear tumors. These findings further support and highlight the importance of selecting a physiologically relevant model based on the type of cancer in which to evaluate the role of specific genes in late tumorigenesis. Finally, single-cell RNA-seq analysis of a previously published dataset in human sporadic cancer, revealed that IL23R was highly expressed in CRC compared to other cancers and specifically in tumor-associated Treg cells.
2024-02-28 | GSE240707 | GEO
Project description:Acquired aplastic anemia (AA) is a rare disease with a complex pathogenesis. In most cases, T cell-mediated immune destruction of hematopoietic cells results in peripheral blood pancytopenia and bone marrow hypoplasia. A subset of the heterodimeric interleukin-23 receptor gene (IL-23R) is significantly associated with autoimmune-mediated diseases. To examine whether IL-23R single nucleotide polymorphisms (SNPs) might contribute to AA, we selected three IL-23R SNPs with amino acid changes (rs11209026: p.Arg381Gln; rs41313262: p.Val362Ile; and rs11465797: p.Thr175Asn) and compared their frequencies in 279 AA patients and 184 ethnically matched healthy controls. The three SNP prevalences were similar between the AA patients and controls. The Arg381Gln variant, which has a strong protective effect against inflammatory bowel disease, showed no association with AA. Furthermore, IL-23 levels in sera were measured in the AA patients and in controls, and there were no significant differences among them. Our results indicate that these three IL-23R SNPs and serum IL-23 level have no apparent impact on susceptibility to AA.
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Project description:Background/aim:IL-23R gene polymorphisms and the association of these polymorphisms with serum IL-23 levels were investigated in patients with psoriasis in the current study. Materials and methods:Sixty-seven patients with psoriasis who were admitted to our dermatology outpatient clinic and 67 healthy controls were included in the study. Polymorphisms of the IL-23R gene were determined by KASP-PCR method, and serum IL-23 levels were determined by ELISA method. Results:The distribution of IL-23R gene polymorphisms rs2201841, rs11209026, rs7530511, rs1343152, and rs11465804 was not significantly different in the patient and control groups. The AA genotype of the rs2201841 locus in males and the GA genotype in females, as well as the AA genotype of the rs1343152 locus in males and the CA genotype in females, were statistically significant in patients with psoriasis. The mean serum IL-23 level was significantly lower in the patient group (42.62 ± 5.96) compared to the control groups (75.76 ± 13.24). Conclusion:IL-23R gene polymorphisms including rs2201841, rs11209026, rs7530511, rs11465804, and rs1343152 were not found to be significantly related to psoriasis. Different genetic polymorphisms may play a role in the development of psoriasis in female and male populations. Ethnic differences between different populations may have led to differences in the distribution of polymorphisms in the current study with compared to other published studies. Additionally, many different genes, polymorphisms, and environmental factors that have an effect on the development of psoriasis may affect the disease process.
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Project description:We found that IL-23R mediated HeLa cell apoptosis by characterizing the functional domains responsible for this event. For exploring apoptotic pathways activated by IL-23R, the altered transcriptomic profiles in responding to IL-23R over-expression was also revealed by RNAseq analysis.
2023-04-06 | GSE229036 | GEO
Project description:The IL-23 receptor (IL-23R) has been found to be associated with small bowel Crohn's disease (CD) in a whole genome association study. Specifically, the rare allele of the R381Q single nucleotide polymorphism (SNP) conferred protection against CD. It is unknown whether IL-23R is associated with IBD in children. The aim was to examine the association of IL-23R with susceptibility to IBD in pediatric patients.DNA was collected from 609 subjects (151 CD and 52 ulcerative colitis [UC] trios). Trios were genotyped for the R381Q SNP of the IL-23R gene and SNP8, SNP12, SNP13, of the CARD15 gene using Taqman. The transmission disequilibrium test (TDT) was used for association to disease using GENEHUNTER 2.0.The rare allele of R381Q SNP was present in 2.7% of CD and 2.9% UC probands. The CARD15 frequency was 31.5% (CD) and 18% (UC). The IL-23R allele was negatively associated with inflammatory bowel disease (IBD): the R381Q SNP was undertransmitted in children with IBD (8 transmitted [T] versus 27 untransmitted [UT]; P = 0.001). This association was significant for all CD patients (6 T versus 19 UT; P = 0.009), especially for non-Jewish CD patients (2 T versus 17 UT; P = 0.0006). TDT showed a borderline association for UC (2 T versus 8 UT; P = 0.06). As expected, CARD15 was associated with CD in children by the TDT (58 T versus 22 UT P = 0.00006), but not with UC.The protective IL-23R R381Q variant was particularly associated with CD in non-Jewish children. Thus, the initial whole genome association study based on ileal CD in adults has been extended to the pediatric population and beyond small bowel CD.
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Project description:Candida albicans 23R genome sequencing project
| PRJNA67711 | ENA
Project description: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.
| S-EPMC6642234 | biostudies-literature
Project description:Inflammatory bowel disease (IBD) is a chronic, complex genetic disease with rapidly increasing prevalence in China. The interactions of genetic, environmental, and microbial factors contribute to the development of IBD, however, the precise etiologies of IBD are not well understood yet. Interleukin-23 receptor (IL-23R) encodes a subunit of receptor for IL-23, which is an important proinflammatory cytokine. In this study, we investigated the relationship between the single nucleotide polymorphism (SNP) of IL-23R gene and IBD in Chinese Han population. We genotyped three nonsynonymous IL-23R SNPs with amino acid changes (rs11209026, p.Arg381Gln; rs41313262 p.Val362Ile and rs11465797 p.Thr175Asn) in 198 patients with IBD (124 UC and 74 CD) and 100 healthy controls. The prevalence of the A allele in IL-23R Arg381Gln of CD appeared less than controls, but it was not statistically significant (2.70% vs. 6.00%, p > 0.05). There was no statistical difference between UC and controls (5.65% vs. 6.00%, p = 0.91). The p.Val362Ile variant was present in 2.42% of UC patients, in 2.70% of CD patients, which was similar in the control (2.00%). There was no statistical difference among these three groups. We did not detect Thr175Asn (rs11465797 c.524 C>A) in all the three groups. In conclusion, our study demonstrated that the p.Val362Ile and Arg381Gln were not associated with susceptibility to IBD in Chinese Han population.
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Project description:While current therapeutic antibodies bind to IL-12 and IL-23 and inhibit their binding to IL-12Rβ1, we describe a novel antibody, termed 6F6, that binds to IL-12 and IL-23 and inhibits the interaction of IL-12 and IL-23 with their cognate signalling receptors IL-12Rβ2 and IL23R. This antibody does not affect the natural inhibition of the IL-12/23 pathway by the antagonists monomeric IL-12p40 and IL-12p80, which suggests that a dual antagonist system is possible. We have mapped the epitope of 6F6 to domain 3 of the p40 chain common to IL-12 and IL-23 and demonstrate that an antibody bound to this epitope is sufficient to inhibit engagement of the signalling receptors. Antibodies with this unique mechanism of inhibition are potent inhibitors of IL-12 induced IFN-γ production and IL-23 induced IL-17 production in vitro, and in an in vivo model of psoriasis, treatment with a humanized variant of this antibody, h6F6, reduced the inflammatory response, resulting in decreased epidermal hyperplasia. We believe that this new class of IL-12/23 neutralising antibodies has the potential to provide improved potency and efficacy as anti-inflammatory agents, particularly in diseases characterized by an overproduction of IL-12.
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