Differentiation of T Helper 17 Cells May Mediate the Abnormal Humoral Immunity in IgA Nephropathy and Inflammatory Bowel Disease Based on Shared Genetic Effects

Qing, Jianbo; Li, Changqun; Hu, Xueli; Song, Wenzhu; Tirichen, Hasna; Yaigoub, Hasnaa; Li, Yafeng

doi:10.3389/fimmu.2022.916934

Cited by 21 publications

(12 citation statements)

References 55 publications

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“…identified CFB, a shared risk locus for the two diseases, that functions in complement activation [ 95 ]. The search for genes susceptible to both diseases is ongoing [ 96–98 ], and our study contributes to the exploration of its potential role. Regarding the prospects in clinical therapeutics, our findings can serve as novel diagnostic biomarkers and clinical treatment guidance for patients with IBD and IgAN.…”

Section: Discussionmentioning

confidence: 99%

Novel immune cross-talk between inflammatory bowel disease and IgA nephropathy

Yan,

Zhao,

Liu

et al. 2024

Renal Failure

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The mechanisms underlying the complex correlation between immunoglobulin A nephropathy (IgAN) and inflammatory bowel disease (IBD) remain unclear. This study aimed to identify the optimal cross-talk genes, potential pathways, and mutual immune-infiltrating microenvironments between IBD and IgAN to elucidate the linkage between patients with IBD and IgAN. The IgAN and IBD datasets were obtained from the Gene Expression Omnibus (GEO). Three algorithms, CIBERSORTx, ssGSEA, and xCell, were used to evaluate the similarities in the infiltrating microenvironment between the two diseases. Weighted gene co-expression network analysis (WGCNA) was implemented in the IBD dataset to identify the major immune infiltration modules, and the Boruta algorithm, RFE algorithm, and LASSO regression were applied to filter the cross-talk genes. Next, multiple machine learning models were applied to confirm the optimal cross-talk genes. Finally, the relevant findings were validated using histology and immunohistochemistry analysis of IBD mice. Immune infiltration analysis showed no significant differences between IBD and IgAN samples in most immune cells. The three algorithms identified 10 diagnostic genes, MAPK3, NFKB1, FDX1, EPHX2, SYNPO, KDF1, METTL7A, RIDA, HSDL2, and RIPK2; FDX1 and NFKB1 were enhanced in the kidney of IBD mice. Kyoto Encyclopedia of Genes and Genomes analysis showed 15 mutual pathways between the two diseases, with lipid metabolism playing a vital role in the cross-talk. Our findings offer insights into the shared immune mechanisms of IgAN and IBD. These common pathways, diagnostic cross-talk genes, and cell-mediated abnormal immunity may inform further experimental studies.

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Section: Discussionmentioning

confidence: 99%

Novel immune cross-talk between inflammatory bowel disease and IgA nephropathy

Yan,

Zhao,

Liu

et al. 2024

Renal Failure

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“…These include Th17 cell differentiation, cellular senescence, and the MAPK and PI3K-Akt signaling pathways. It has been shown that the abnormal humoral immunity observed in IgA nephropathy may be mediated by the differentiation of T helper 17 cells [9] and kidney senescence is well documented to occur after injury [10]. It has been observed that Akt activation is increased in experimental tubulointerstitial fibrosis [11, 12].…”

Section: Discussionmentioning

confidence: 99%

Identification of inflammatory biomarkers in IgA nephropathy using the NanoString technology: a validation study

Gaumond,

Lamarche,

Beauchemin

et al. 2023

Preprint

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Objective and design: Immunoglobulin A nephropathy (IgAN) is a kidney disease characterized by the accumulation of IgA deposits in the glomeruli of the kidney, leading to inflammation and damage to the kidney. The inflammatory markers involved in IgAN remain to be defined. Gene expression analysis platforms, such as the NanoString nCounter system, are promising screening and diagnostic tools, especially in the oncology field, but its role as a diagnostic and prognostic tool in IgAN remains scarce. In this study, we aimed to validate the use of NanoString technology to identify potential inflammatory biomarkers involved in the progression of IgAN. Subjects: A total of 30 patients with biopsy-proven IgAN and 7 cases of antineutrophil cytoplasmic antoantibodies (ANCA) associated pauci-immune glomerulonephritis were included for gene expression measurement. For the immunofluorescence validation experiments, a total of 6 IgAN patients and 3 healthy controls were included. Methods: Total RNA was extracted from formalin-fixed-paraffin-embedded kidney biopsy specimens, and a customized 48-plex human gene CodeSet was used to study 29 genes implicated in different biological pathways. Comparisons in gene expression were made between IgAN and ANCA-associated pauci-immune glomerulonephritis patients to delineate an expression profile specific to IgAN. Gene expression was compared between patients with low and moderate risk of progression. Genes for which RNA expression was associated with disease progression were analyzed for protein expression by immunofluorescence, and compared with healthy controls. Results: IgAN patients had a distinct gene expression profile with decreased expression in genes IL-6, INFG and C1QB compared to ANCA patients. C3 and TNFR2 were identified as potential biomarkers for IgAN progression in patients early in their disease course. Protein expression for those 2 candidate genes was upregulated in IgAN patients compared to controls. Expression of genes implicated in fibrosis (PTEN, CASPASE 3, TGM2, TGFB1, IL2, and TNFRSF1B) was more pronounced in IgAN patient with severe fibrosis compared to those with none. Conclusions: Our findings validate our NanoString mRNA profiling by examining protein expression levels of two candidate genes, C3 and TNFR2, in IgAN patients and healthy controls. We were also able to identify several upregulated mRNA transcripts implicated in the development of fibrosis that may be considered as fibrotic markers within IgAN patients.

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“…The results of the analysis showed that there were 11 types of immune cells with significant differences in the degree of infiltration between SCM myocardial tissue and normal tissue. Th17 cells play an important role in the regulation of immune-related diseases ( 42 ), and previous findings suggest that an increase in neutrophils and Th17 cells may lead to a decrease in immune system defenses in patients with sepsis ( 43 , 44 ); Studies on Tfh cells have shown that Tfh cells are associated with mortality warnings in patients with sepsis, and low Tfh cell levels may imply a poor prognosis for patients ( 45 ); Danahy et al 's research shows that in sepsis, not only the total number of CD8 + T cells decreases, but also the antigen-driven proliferation capacity and effector function of CD8 + T cells are also impaired ( 46 ); These are consistent with the results of our immune infiltration analysis, which further confirmed the important role of abnormal immune response in the pathogenesis and progression of SCM.…”

Section: Discussionmentioning

confidence: 99%

Identification of immune-related hub genes and miRNA-mRNA pairs involved in immune infiltration in human septic cardiomyopathy by bioinformatics analysis

Sun²,

Ma³

et al. 2022

Front. Cardiovasc. Med.

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Septic cardiomyopathy (SCM) is a serious complication caused by sepsis that will further exacerbate the patient's prognosis. However, immune-related genes (IRGs) and their molecular mechanism during septic cardiomyopathy are largely unknown. Therefore, our study aims to explore the immune-related hub genes (IRHGs) and immune-related miRNA-mRNA pairs with potential biological regulation in SCM by means of bioinformatics analysis and experimental validation.MethodFirstly, screen differentially expressed mRNAs (DE-mRNAs) from the dataset GSE79962, and construct a PPI network of DE-mRNAs. Secondly, the hub genes of SCM were identified from the PPI network and the hub genes were overlapped with immune cell marker genes (ICMGs) to further obtain IRHGs in SCM. In addition, receiver operating characteristic (ROC) curve analysis was also performed in this process to determine the disease diagnostic capability of IRHGs. Finally, the crucial miRNA-IRHG regulatory network of IRHGs was predicted and constructed by bioinformatic methods. Real-time quantitative reverse transcription-PCR (qRT-PCR) and dataset GSE72380 were used to validate the expression of the key miRNA-IRHG axis.ResultThe results of immune infiltration showed that neutrophils, Th17 cells, Tfh cells, and central memory cells in SCM had more infiltration than the control group; A total of 2 IRHGs were obtained by crossing the hub gene with the ICMGs, and the IRHGs were validated by dataset and qRT-PCR. Ultimately, we obtained the IRHG in SCM: THBS1. The ROC curve results of THBS1 showed that the area under the curve (AUC) was 0.909. Finally, the miR-222-3p/THBS1 axis regulatory network was constructed.ConclusionIn summary, we propose that THBS1 may be a key IRHG, and can serve as a biomarker for the diagnosis of SCM; in addition, the immune-related regulatory network miR-222-3p/THBS1 may be involved in the regulation of the pathogenesis of SCM and may serve as a promising candidate for SCM therapy.

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Differentiation of T Helper 17 Cells May Mediate the Abnormal Humoral Immunity in IgA Nephropathy and Inflammatory Bowel Disease Based on Shared Genetic Effects

Cited by 21 publications

References 55 publications

Novel immune cross-talk between inflammatory bowel disease and IgA nephropathy

Novel immune cross-talk between inflammatory bowel disease and IgA nephropathy

Identification of inflammatory biomarkers in IgA nephropathy using the NanoString technology: a validation study

Identification of immune-related hub genes and miRNA-mRNA pairs involved in immune infiltration in human septic cardiomyopathy by bioinformatics analysis

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