X‐linked inhibitor of apoptosis‐associated factor 1 regulates TNF receptor 1 complex stability

Lin, Boren; Xu, Da; Leaman, Douglas W.

doi:10.1002/1873-3468.12467

Cited by 3 publications

(3 citation statements)

References 51 publications

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“…Interestingly, we observed a lower expression of TNF receptor superfamily member 25 (TNFRSF25), TNF receptor superfamily member 1A (TNFRSF1A) and IL-3 receptor IL-3RA genes that are associated with the stability of Tregs (Figure 5h). [77][78][79] Finally, we found a higher activity for IFN-a and IFN-b, IFN regulatory factor 7 (IRF7) and CD40L upstream regulators in Tregs from ART than in Tregs from LTNPs (Figure 5i). IFN-a/b signalling promotes Treg development and function, which occurs through key transcriptional regulators such as IRF7 and IRF9.…”

Section: High Ppar Signalling Results In a Lower Stat3 In Tregs Of Ltnpsmentioning

confidence: 98%

“…This was accompanied by the upregulation of several genes related to apoptosis in Tregs from ARTs, such as BCL-2-interacting protein 3 (BNIP3), XIAP, BCL-2-associated transcription factor 1 (BCLAF1), FAS and caspases 2, 7, 8, 10 and 14 (Figure 6h). 77,[85][86][87] Apoptotic Tregs release ATP that is converted to adenosine through the tandem function of CD39 and CD73, two ectoenzymes that are expressed on the surface of Tregs. 85 Contrary to previous reports, 46 we did not find any significant difference in the expression of CD39 on Tregs of different study groups (Figure 6i and Supplementary figure 4a).…”

Section: Tregs From Art Exhibit More Suppressive Properties Compared To Their Counterparts In Hcs and Ltnpsmentioning

confidence: 99%

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Differential transcriptional and functional properties of regulatory T cells in HIV‐infected individuals on antiretroviral therapy and long‐term non‐progressors

2021

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Objectives Regulatory T cells (Tregs) are widely recognised as a subset of CD4+CD25+FOXP3+ T cells that have a key role in maintaining immune homeostasis. The impact of HIV‐1 infection on immunological properties and effector functions of Tregs has remained the topic of debate and controversy. In the present study, we investigated transcriptional profile and functional properties of Tregs in HIV‐1‐infected individuals either receiving antiretroviral therapy (ART, n = 50) or long‐term non‐progressors (LTNPs, n = 24) compared to healthy controls (HCs, n = 38). Methods RNA sequencing (RNAseq), flow cytometry‐based immunophenotyping and functional assays were performed to study Tregs in different HIV cohorts. Results Our RNAseq analysis revealed that Tregs exhibit different transcriptional profiles in HIV‐infected individuals. While Tregs from patients on ART upregulate pathways associated with a more suppressive (activated) phenotype, Tregs in LTNPs exhibit upregulation of pathways associated with impaired suppressive properties. These observations may explain a higher propensity for autoimmune diseases in LTNPs. Also, we found substantial upregulation of HLA‐F mRNA and HLA‐F protein in Tregs from HIV‐infected subjects compared to healthy individuals. These observations highlight a potential role for this non‐classical HLA in Tregs in the context of HIV infection, which should be investigated further in other chronic viral infections and cancer. Conclusion Our study has provided a novel insight into Tregs at the transcriptional and functional levels in different HIV‐infected groups.

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Section: High Ppar Signalling Results In a Lower Stat3 In Tregs Of Ltnpsmentioning

confidence: 98%

Section: Tregs From Art Exhibit More Suppressive Properties Compared To Their Counterparts In Hcs and Ltnpsmentioning

confidence: 99%

Differential transcriptional and functional properties of regulatory T cells in HIV‐infected individuals on antiretroviral therapy and long‐term non‐progressors

2021

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“…32,33 XAF1 is regarded as a novel binding ligand of XIAP that can reverse the antiapoptotic effect of XIAP. 34 A single-cell sequencing study of single nucleated cells in the peripheral blood from patients with COVID-19 and influenza revealed that XAF1 expression is upregulated in COVID-19 patients and that the XAF1induced increase in T-cell apoptosis may be associated with the TNFα/TNFR1 and Fas/FasL pathways. 35 To further study the expression of the six genes after SARS-CoV-2 infection, we analyzed the changes in their expression with the time of infection in the lung tissue sequencing data of SARS-CoV-2infected mice and found that their expression in the lung tissue increased after SARS-CoV-2 infection.…”

Section: Discussionmentioning

confidence: 99%

Genome‐wide screening of SARS‐CoV‐2 infection‐related genes based on the blood leukocytes sequencing data set of patients with COVID‐19

Gào

Liu

Zou

et al. 2021

Journal of Medical Virology

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Coronavirus disease 2019 (COVID‐19) is a global epidemic disease caused by a novel virus, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), causing serious adverse effects on human health. In this study, we obtained a blood leukocytes sequencing data set of COVID‐19 patients from the GEO database and obtained differentially expressed genes (DEGs). We further analyzed these DEGs by protein–protein interaction analysis and Gene Ontology enrichment analysis and identified the DEGs closely related to SARS‐CoV‐2 infection. Then, we constructed a six‐gene model (comprising IFIT3, OASL, USP18, XAF1, IFI27 , and EPSTI1 ) by logistic regression analysis and calculated the area under the ROC curve (AUC) for the diagnosis of COVID‐19. The AUC values of the training group, testing group, and entire group were 0.930, 0.914, and 0.921, respectively. The six genes were highly expressed in patients with COVID‐19 and positively correlated with the expression of SARS‐CoV‐2 invasion‐related genes ( ACE2, TMPRSS2, CTSB , and CTSL ). The risk score calculated by this model was also positively correlated with the expression of TMPRSS2, CTSB , and CTSL , indicating that the six genes were closely related to SARS‐CoV‐2 infection. In conclusion, we comprehensively analyzed the functions of DEGs in the blood leukocytes of patients with COVID‐19 and constructed a six‐gene model that may contribute to the development of new diagnostic and therapeutic ideas for COVID‐19. Moreover, these six genes may be therapeutic targets for COVID‐19.

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P2X7 receptor blockade prevents preterm birth and perinatal brain injury in a mouse model of intrauterine inflammation†

Tsimis

Lei

Rosenzweig

et al. 2017

Biology of Reproduction

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The P2X7 is an adenosine triphosphate (ATP)-gated ion channel involved in several facets of immune activation and neuronal function through its importance in interleukin (IL)-1β secretion. We hypothesized that blockade of P2X7 would prevent perinatal brain injury associated with exposure to intrauterine (IU) inflammation. Dams received 45 mg/kg of Brilliant Blue G (BBG), a specific P2X7 receptor (P2X7R) antagonist, on gestation day 17 (E17) prior to administration of lipopolysaccharide (LPS) or phosphate-buffered saline (PBS). Furthermore, we utilized embryo transfer experiments to delineate whether the P2X7 was the key mediator of IU inflammation-associated brain injury on maternal or fetal sides. In these experiments, P2X7-/- dams were embryo-transferred wild type embryos and wild type dams were embryo-transferred P2X7-/- embryos. In the mouse model of intrauterine inflammation, pharmacologic blockade of P2X7R reduced preterm birth rate, improved offspring performance on neuromotor tests as well as the dendritic arborization and density of cortical neurons. Embryo transfer experiments demonstrated the importance of maternal P2X7R in IU inflammation-mediated effects on offspring. Both genetic and pharmacologic blockade of IL-1β signaling, by targeting maternal P2X7R, ameliorated perinatal brain injury following exposure to IU inflammation. Specific targeting of maternal P2X7R may provide a clinically useful tool to prevent both preterm birth and prematurity-associated perinatal brain injury, and further studies are urgently needed.

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X‐linked inhibitor of apoptosis‐associated factor 1 regulates TNF receptor 1 complex stability

Cited by 3 publications

References 51 publications

Differential transcriptional and functional properties of regulatory T cells in HIV‐infected individuals on antiretroviral therapy and long‐term non‐progressors

Differential transcriptional and functional properties of regulatory T cells in HIV‐infected individuals on antiretroviral therapy and long‐term non‐progressors

Genome‐wide screening of SARS‐CoV‐2 infection‐related genes based on the blood leukocytes sequencing data set of patients with COVID‐19

P2X7 receptor blockade prevents preterm birth and perinatal brain injury in a mouse model of intrauterine inflammation†

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