CCAAT/Enhancer-Binding Protein α Negatively Regulates IFN-γ Expression in T Cells

Tanaka, Shinya; Tanaka, Kentaro; Magnusson, Fay; Chung, Yeonseok; Martínez, Gustavo; Wang, Yi Hong; Nurieva, Roza; Kurosaki, Tomohiro; Dong, Chen

doi:10.4049/jimmunol.1303422

Cited by 23 publications

(17 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4B). C/EBPa can inhibit Th1 and Th17 cell differentiation; moreover, enhanced IFN-g and IL-17 expression were observed in Cebpa KO CD4 + T cells (15). A mechanism study revealed that C/EBPa could bind to the Ifng gene and inhibited T-bet-driven Ifng transcription (15).…”

Section: Negative Regulators Of Immune Cell Subpopulations Can Be Idementioning

confidence: 99%

Virtual Sorting Has a Distinctive Advantage in Identification of Anticorrelated Genes and Further Negative Regulators of Immune Cell Subpopulations

Wang

Han

2017

The Journal of Immunology

View full text Add to dashboard Cite

Immune cells are highly plastic in both gene expression and cell phenotype. We have established a method of gene expressional plasticity and virtual sorting to evaluate immune cell subpopulations and their characteristic genes in human CD4 T cells. In this study, we continued to investigate the informatics mechanism on the effectiveness of virtual sorting. We found that virtual sorting had an overall positive correlation to the Pearson correlation in the identification of positively correlated genes. However, owing to nonlinear biological anticorrelation, virtual sorting showed a distinctive advantage for anticorrelated genes, suggesting an important role in the identification of negative regulators. In addition, based on virtual sorting results, we identified two basic gene sets among highly plastic genes, i.e., highly plastic cell cycle-associated molecules and highly plastic immune and defense response-associated molecules. Genes within each set tended to be positively connected, but genes between two sets were often anticorrelated. Further analysis revealed preferential transcription factor binding motifs existed between highly plastic cell cycle-associated molecules and highly plastic immune and defense response-associated molecules. Our results strongly suggested predetermined regulation, which was called an immune cell internal phenotype, should exist and could be mined by virtual sorting analysis. This provided efficient functional clues to study immune cell phenotypes and their regulation. Moreover, the current substantial virtual sorting results in both CD4 T cells and B cells provide a useful resource for big-data-driven experimental studies and knowledge discoveries.

show abstract

Section: Negative Regulators Of Immune Cell Subpopulations Can Be Idementioning

confidence: 99%

Virtual Sorting Has a Distinctive Advantage in Identification of Anticorrelated Genes and Further Negative Regulators of Immune Cell Subpopulations

Wang

Han

2017

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…The predicted pathways are presented as circular networks with the transcripts on the circumference and the transcription factors, cytokines and transmembrane receptors enriched by in silico IPA network growth in the centre. The 293 transcripts overexpressed in responders were connected to molecules involved in Th2 ( CSF3, IL4, IL5, IL18 and SPI1, red circles) and Th1 responses ( STAT1, STAT4, IL2 and SMARCR4, blue circles) and their regulation ( CEBPA, purple circle) 43 (Figure 5A). The 496 transcripts underexpressed in responders were connected to molecules involved in the suppression of inflammation ( TWIST1, FOXO1, FOXO3, TP53, CTNNB1 and SIM 1, red circles) (Figure 5B), which is in line with the data in Figures 2 and 4.…”

Section: Resultsmentioning

confidence: 99%

Whole blood transcriptional variations between responders and non‐responders in asthma patients receiving omalizumab

Upchurch

Wiest

Cardenas

et al. 2020

Clin Experimental Allergy

View full text Add to dashboard Cite

Background Anti‐IgE (omalizumab) has been used for the treatment of moderate‐to‐severe asthma that is not controlled by inhaled steroids. Despite its success, it does not always provide patients with significant clinical benefits. Objective To investigate the transcriptional variations between omalizumab responders and non‐responders and to study the mechanisms of action of omalizumab. Methods The whole blood transcriptomes of moderate‐to‐severe adult asthma patients (N = 45:34 responders and 11 non‐responders) were analysed over the course of omalizumab treatment. Non‐asthmatic healthy controls (N = 17) were used as controls. Results Transcriptome variations between responders and non‐responders were identified using the genes significant (FDR < 0.05) in at least one comparison of each patient response status and time point compared with control subjects. Using gene ontology and network analysis, eight clusters of genes were identified. Longitudinal analyses of individual clusters revealed that responders could maintain changes induced with omalizumab treatment and become more similar to the control subjects, while non‐responders tend to remain more similar to their pre‐treatment baseline. Further analysis of an inflammatory gene cluster revealed that genes associated with neutrophil/eosinophil activities were up‐regulated in non‐responders and, more importantly, omalizumab did not significantly alter their expression levels. The application of modular analysis supported our findings and further revealed variations between responders and non‐responders. Conclusion and Clinical Relevance This study provides not only transcriptional variations between omalizumab responders and non‐responders, but also molecular insights for controlling asthma by omalizumab.

show abstract

“…Bcl6 regulatory activity was detected in lung TFH-like cluster 3 and LN TFH cluster 3, alongwith Cebpa, which is reported to inhibit both IFNγ production and TCR-driven proliferation ( Supplementary Fig. 2i) 30,31 . Interestingly, Foxp3-associated regulatory activity was enriched in lung over LN although there was only minimal expression of 9 Foxp3 transcript in the data set and Foxp3+ cells were not detected by FACS in the antigen-specific compartment ( Supplementary Fig.…”

mentioning

confidence: 99%

Redefining CD4 T cell residency: Helper T cells orchestrate protective humoral immunity in the lung

Swarnalekha

Schreiner

Litzler

et al. 2020

Preprint

View full text Add to dashboard Cite

Influenza is a severe and acute respiratory pathogen, and a significant cause for morbidity, particularly in young children and the elderly. Following influenza infection, clonally expanded T cells take up permanent residence in the lung where they are poised to rapidly respond to challenge infection. The non-circulating status of these tissue resident memory (TRM) cells makes them an attractive target for vaccination. While many studies have characterized CD8 TRM cells, less is known about the heterogeneity and protective capacity of CD4 TRM cells. Here we characterized the dynamics and transcriptional regulation of lung resident CD4 T cells to define a nonlymphoid signature that removes the bias created by the prevalence of Th1 helper cells during viral infection. We identified a novel population of long-lived T resident helper (TRH) cells that requires intrinsic Bcl6 expression for their differentiation. Although TRH cells also depend on B cells, they are generated independently of T follicular helper effector cells in the lymph node. In contrast to lung resident Th1 cells, TRH cells are tightly co-localized with B cells in inducible Bronchus Associated Lymphoid Tissue (iBALT). Deletion of Bcl6 in CD4 T cells prior to heterotypic challenge infection results in redistribution of CD4 T cells outside of iBALT areas and impaired local antibody production. These data highlight lung iBALT as a niche for the homeostasis and survival of TRH cells, and further suggest that vaccination strategies to selectively induce TRH cells can improve protective immunity in the tissue.2 MainSeasonal influenza epidemics are a major cause of global morbidity and mortality. Although annually administered influenza vaccines are among the most widely used in the world, vaccine-elicited neutralizing antibodies offer poor protection against new influenza strains 1 . In contrast, there is evidence that prior influenza infection can accelerate viral clearance after heterotypic infection in both mice and humans 2,3,4,5,6 . Emerging data suggests that the targeted generation of CD4 memory T cells recognizing conserved epitopes from internal viral proteins may form the basis of a universal influenza virus vaccine 7,8 . CD4 memory T cells are induced following immunization or infection and can be recalled to generate secondary effectors during a challenge infection. Several subsets of CD4 memory cells have been described, including central memory (TCM) and effector memory (TEM) cells which circulate through secondary lymphoid and non-lymphoid tissues 9 . More recently, tissue resident memory (TRM) cells that persist in barrier tissues such as lung and skin have been described 10 . Although CD4 T cells actually outnumber CD8 T cells in barrier tissues, the majority of studies have focused on the requirements for CD8 TRM cell differentiation. In addition, although CD4 T cells are renowned for their substantial plasticity during immune responses, less is known about diversification within the CD4 TRM cell compartment 11,12,13,14,15,16 .Influenza i...

show abstract

CCAAT/Enhancer-Binding Protein α Negatively Regulates IFN-γ Expression in T Cells

Cited by 23 publications

References 36 publications

Virtual Sorting Has a Distinctive Advantage in Identification of Anticorrelated Genes and Further Negative Regulators of Immune Cell Subpopulations

Virtual Sorting Has a Distinctive Advantage in Identification of Anticorrelated Genes and Further Negative Regulators of Immune Cell Subpopulations

Whole blood transcriptional variations between responders and non‐responders in asthma patients receiving omalizumab

Redefining CD4 T cell residency: Helper T cells orchestrate protective humoral immunity in the lung

Contact Info

Product

Resources

About