IRF8: identity-keeper for suppressive Th1-like Treg cells

Lee, Gap Ryol

doi:10.1038/s41423-018-0044-9

Cited by 4 publications

(2 citation statements)

References 20 publications

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“…S12, http://links.lww.com/HC9/A236 ). This module was enriched for KRAS, IL-6, IL-2 signalling, and TNF signalling; and contained the hub gene, IRF8 , the identity-keeper for suppressive T H 1-like T REG cells 34 (Fig. S12H, http://links.lww.com/HC9/A236 ).…”

Section: Resultsmentioning

confidence: 99%

Regulation of immune responses in primary biliary cholangitis: a transcriptomic analysis of peripheral immune cells

Mulcahy

Liaskou

Martin

et al. 2023

Hepatology Communications

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Background & Aims: In patients with primary biliary cholangitis (PBC), the serum liver biochemistry measured during treatment with ursodeoxycholic acid—the UDCA response—accurately predicts long-term outcome. Molecular characterization of patients stratified by UDCA response can improve biological understanding of the high-risk disease, thereby helping to identify alternative approaches to disease-modifying therapy. In this study, we sought to characterize the immunobiology of the UDCA response using transcriptional profiling of peripheral blood mononuclear cell subsets. Methods: We performed bulk RNA-sequencing of monocytes and TH1, TH17, TREG, and B cells isolated from the peripheral blood of 15 PBC patients with adequate UDCA response (“responders”), 16 PBC patients with inadequate UDCA response (“nonresponders”), and 15 matched controls. We used the Weighted Gene Co-expression Network Analysis to identify networks of co-expressed genes (“modules”) associated with response status and the most highly connected genes (“hub genes”) within them. Finally, we performed a Multi-Omics Factor Analysis of the Weighted Gene Co-expression Network Analysis modules to identify the principal axes of biological variation (“latent factors”) across all peripheral blood mononuclear cell subsets. Results: Using the Weighted Gene Co-expression Network Analysis, we identified modules associated with response and/or disease status (q<0.05) in each peripheral blood mononuclear cell subset. Hub genes and functional annotations suggested that monocytes are proinflammatory in nonresponders, but antiinflammatory in responders; TH1 and TH17 cells are activated in all PBC cases but better regulated in responders; and TREG cells are activated—but also kept in check—in responders. Using the Multi-Omics Factor Analysis, we found that antiinflammatory activity in monocytes, regulation of TH1 cells, and activation of TREG cells are interrelated and more prominent in responders. Conclusions: We provide evidence that adaptive immune responses are better regulated in patients with PBC with adequate UDCA response.

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Section: Resultsmentioning

confidence: 99%

Regulation of immune responses in primary biliary cholangitis: a transcriptomic analysis of peripheral immune cells

Mulcahy

Liaskou

Martin

et al. 2023

Hepatology Communications

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show abstract

“…COPD-related T-regs showed a high enrichment on IRF8. Highly IRF8 expression in T-regs controlled the type response and IRF8 is an identity-keeper for suppressive Th1-like T-regs 32 . And LCCOPD-elated T-regs showed a high enrichment on IRF4 and IRF5.…”

Section: Tissue-speci C T-reg Cells Showed Signi Cant Changes In Meta...mentioning

confidence: 99%

Single-cell RNA Sequencing Reveals the Tissue-specific Immune Signatures of Lung Cancer with COPD Overlapped

Meng

Chang#

Wang#

et al. 2022

Preprint

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COPD is one of the high-risk factors for lung cancer, but the underlying mechanism is still unclear. Here, we performed single-cell RNA sequencing analysis on three COPD tissues, and three COPD-based lung cancer tissue (LCCOPD), and enrolled the scRNA-seq data of normal lung tissues, COPD tissues, lung cancer tissues, and LCCOPD tissues from the public database. We found that most immune cell types were significantly enriched in COPD groups, and the LCCOPD showed a differential enrichment of T-regs and macrophage subtypes in comparison with COPD. FOXP3 mRNA expression was significantly increased in LCOPD-related T-regs and positively associated with CTLA-4 and PD-1 to form an immunosuppressive environment. Macrophages from different pathological environments show significant differences in cell composition, pseudo-time trajectories, and phenotypic dominance. COPD-related macrophages were dominated by M1-type with increased cell proliferation. LCCOPD-related macrophages, dominated by M2-type and tumor-associated macrophages, had progressively enhanced immune population chemotaxis along the trajectory. Based on the public data, we found the overlap of COPD accelerated infiltration of T-regs and M2 macrophages. Several metabolic and cytokine pathways were down-regulated in COPD tissues and up-regulated in LCCOPD groups, such as the SREBP pathway, IL2, IFN-γ, glycolysis, and glutamine metabolism. Our study provided an extensive description of lung cancer overlapping COPD and revealed the association between COPD status and the formation of an immunosuppressive environment, which elucidates the role of COPD, as a high-risk factor, in the development of lung cancer.

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Promoted Generation of T Helper 1-Like Regulatory T Cells After Transient Middle Cerebral Artery Occlusion in Type-2 Diabetic Mice

Jiang

Gao

et al. 2023

Immunological Investigations

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IRF8: identity-keeper for suppressive Th1-like Treg cells

Cited by 4 publications

References 20 publications

Regulation of immune responses in primary biliary cholangitis: a transcriptomic analysis of peripheral immune cells

Regulation of immune responses in primary biliary cholangitis: a transcriptomic analysis of peripheral immune cells

Single-cell RNA Sequencing Reveals the Tissue-specific Immune Signatures of Lung Cancer with COPD Overlapped

Promoted Generation of T Helper 1-Like Regulatory T Cells After Transient Middle Cerebral Artery Occlusion in Type-2 Diabetic Mice

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