Developing T cells form an immunological synapse for passage through the β-selection checkpoint

Allam, Amr H.; Charnley, Mirren; Pham, Kim; Russell, Sarah M.

doi:10.1083/jcb.201908108

Cited by 19 publications

(35 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other DEGs common to both cohorts include copine 3 or 6 (CPNE3/6) which are components of the ciliary body, and affects neural plasticity, but coincidentally, reduced CPNE3 expression is associated with the risk of acute MI and stable CAD [ 77 ]. A potential connection between these cilia/synaptic transcripts and the Treg changes in atherosclerosis is that the maturation of Tregs likely depends on proper immune synapse formation in maturing T cells [ 78 ].…”

Section: Resultsmentioning

confidence: 99%

RNA sequencing of blood in coronary artery disease: involvement of regulatory T cell imbalance

et al. 2021

View full text Add to dashboard Cite

Background Cardiovascular disease had a global prevalence of 523 million cases and 18.6 million deaths in 2019. The current standard for diagnosing coronary artery disease (CAD) is coronary angiography. Surprisingly, despite well-established clinical indications, up to 40% of the one million invasive cardiac catheterizations return a result of ‘no blockage’. The present studies employed RNA sequencing of whole blood to identify an RNA signature in patients with angiographically confirmed CAD. Methods Whole blood RNA was depleted of ribosomal RNA (rRNA) and analyzed by single-molecule sequencing of RNA (RNAseq) to identify transcripts associated with CAD (TRACs) in a discovery group of 96 patients presenting for elective coronary catheterization. The resulting transcript counts were compared between groups to identify differentially expressed genes (DEGs). Results Surprisingly, 98% of DEGs/TRACs were down-regulated ~ 1.7-fold in patients with mild to severe CAD (> 20% stenosis). The TRACs were independent of comorbid risk factors for CAD, such as sex, hypertension, and smoking. Bioinformatic analysis identified an enrichment in transcripts such as FoxP1, ICOSLG, IKZF4/Eos, SMYD3, TRIM28, and TCF3/E2A that are likely markers of regulatory T cells (Treg), consistent with known reductions in Tregs in CAD. A validation cohort of 80 patients confirmed the overall pattern (92% down-regulation) and supported many of the Treg-related changes. TRACs were enriched for transcripts associated with stress granules, which sequester RNAs, and ciliary and synaptic transcripts, possibly consistent with changes in the immune synapse of developing T cells. Conclusions These studies identify a novel mRNA signature of a Treg-like defect in CAD patients and provides a blueprint for a diagnostic test for CAD. The pattern of changes is consistent with stress-related changes in the maturation of T and Treg cells, possibly due to changes in the immune synapse.

show abstract

Section: Resultsmentioning

confidence: 99%

RNA sequencing of blood in coronary artery disease: involvement of regulatory T cell imbalance

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Other DEGs common to both cohorts include copine 3 or 6 (CPNE3/6) which are components of the ciliary body, and affects neural plasticity, but coincidentally, reduced CPNE3 expression is associated with the risk of acute MI and stable CAD [76]. A potential connection between these cilia/synaptic transcripts and the Treg changes in atherosclerosis is that the maturation of Tregs likely depends on proper immune synapse formation in maturing T cells [77].…”

Section: 22mentioning

confidence: 99%

RNA Sequencing of Blood in Coronary Artery Disease: Involvement of Regulatory T Cell Imbalance

McCaffrey

Toma

Yang

et al. 2021

Preprint

View full text Add to dashboard Cite

RATIONALE: Cardiovascular disease had a global prevalence of 523 million cases and 18.6 million deaths in 2019. The current standard for diagnosing coronary artery disease (CAD) is coronary angiography. Surprisingly, despite well-established clinical indications, up to 40% of the one million invasive cardiac catheterizations return a result of ‘no blockage’. OBJECTIVE: The present studies employed RNA sequencing of whole blood to identify an RNA signature in patients presenting with a clinical suspicion of CAD.METHODS AND RESULTS: Whole blood RNA was depleted of ribosomal RNA (rRNA) and analyzed by single-molecule sequencing of RNA (RNAseq) to identify transcripts associated with CAD (TRACs) in a discovery group of 96 patients presenting for elective coronary catheterization. The resulting transcript counts were compared between groups to identify differentially expressed genes (DEGs). Surprisingly, 98% of DEGs/TRACs were down-regulated ~1.7-fold in patients with mild to severe CAD (>20% stenosis). The TRACs were independent of comorbid risk factors for CAD, such as gender, hypertension, and smoking. Bioinformatic analysis identified an enrichment in transcripts such as FoxP1, ICOSLG, IKZF4/Eos, SMYD3, TRIM28, and TCF3/E2A that are likely markers of regulatory T cells (Treg), consistent with known reductions in Tregs in CAD. A validation cohort of 80 patients confirmed the overall pattern (92% down-regulation) and supported many of the Treg-related changes. TRACs were enriched for transcripts associated with stress granules, which sequester RNAs, and ciliary and synaptic transcripts, possibly consistent with changes in the immune synapse of developing T cells.CONCLUSIONS: These studies identify a novel mRNA signature of a Treg-like defect in CAD patients and provides a blueprint for a diagnostic test for CAD. The pattern of changes is consistent with stress-related changes in the maturation of T and Treg cells, possibly due to changes in the immune synapse.

show abstract

“…High-speed 3D imaging in the millisecond regime is a muchneeded tool to tackle the challenge of imaging across scales. For example, high-speed axial scanning would allow robust 3D tracking of cytoskeletal dynamics near the immunological synapse in nonadherent and floating immune cells (Allam et al, 2021;Kumari et al, 2020) (Fig. 1A).…”

Section: Introductionmentioning

confidence: 99%

Electrically tunable lenses – eliminating mechanical axial movements during high-speed 3D live imaging

Efstathiou

Draviam

2021

Journal of Cell Science

View full text Add to dashboard Cite

The successful investigation of photosensitive and dynamic biological events, such as those in a proliferating tissue or a dividing cell, requires non-intervening high-speed imaging techniques. Electrically tunable lenses (ETLs) are liquid lenses possessing shape-changing capabilities that enable rapid axial shifts of the focal plane, in turn achieving acquisition speeds within the millisecond regime. These human-eye-inspired liquid lenses can enable fast focusing and have been applied in a variety of cell biology studies. Here, we review the history, opportunities and challenges underpinning the use of cost-effective high-speed ETLs. Although other, more expensive solutions for three-dimensional imaging in the millisecond regime are available, ETLs continue to be a powerful, yet inexpensive, contender for live-cell microscopy.

show abstract

Developing T cells form an immunological synapse for passage through the β-selection checkpoint

Cited by 19 publications

References 67 publications

RNA sequencing of blood in coronary artery disease: involvement of regulatory T cell imbalance

RNA sequencing of blood in coronary artery disease: involvement of regulatory T cell imbalance

RNA Sequencing of Blood in Coronary Artery Disease: Involvement of Regulatory T Cell Imbalance

Electrically tunable lenses – eliminating mechanical axial movements during high-speed 3D live imaging

Contact Info

Product

Resources

About