Endothelial cell and T‐cell crosstalk: Targeting metabolism as a therapeutic approach in chronic inflammation

Certo, Michelangelo; Elkafrawy, Hagar; Pucino, Valentina; Cucchi, Danilo; Cheung, Katherine; Mauro, Claudio

doi:10.1111/bph.15002

Cited by 35 publications

(18 citation statements)

References 163 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Endothelial cells are one of the main components of the retinal microvasculature, which is essential for retinal function (34). They play an important role in both inflammation and angiogenesis in DR (15) and are critical in attracting immune cells to sites of inflammation (35). Inflammatory cells produce angiogenic cytokines and growth factors, which in turn activate the microvascular endothelium, which expresses pro-inflammatory molecules (36)(37)(38).…”

Section: Discussionmentioning

confidence: 99%

Single-cell transcriptomic analysis revealing changes in retinal cell subpopulation levels and the pathways involved in diabetic retinopathy

Zhang¹,

Huang

Chen

et al. 2022

Ann Transl Med

View full text Add to dashboard Cite

Background: Diabetic retinopathy (DR) is a common microvascular complication of diabetes and one of the most common causes of visual impairment and blindness. However, it is not yet known how abnormal retinal cell subpopulations contribute to disease progression.Methods: In this study, we used the Gene Expression Omnibus database to construct a single-cell atlas of DR and healthy samples to explore changes in the abundance of different cell subpopulations, and identify the molecular pathways potentially involved in DR.Results: Our results showed that DR was associated with significantly reduced numbers of bipolar cells, Müller glia, retinal pigment epithelial cells, and cone photoreceptors, but was also associated with significantly greater numbers of pericytes, rod photoreceptors, anaplastic cells, and microglia. Our results suggest that subpopulations of Müller glia, microglia, endothelial cells, and bipolar cells in DR tissues may be involved in various oxidative stress-and inflammation-related pathways.Conclusions: In summary, we showed that Müller glia, endothelial cells, microglia, and bipolar cells in DR tissues are involved in oxidative stress-and inflammation-related pathways, which may contribute to the progression of the disease and ultimately lead to visual impairment and blindness. This study will provide a theoretical basis for further exploring the specific mechanism of DR.

show abstract

Section: Discussionmentioning

confidence: 99%

Single-cell transcriptomic analysis revealing changes in retinal cell subpopulation levels and the pathways involved in diabetic retinopathy

Zhang¹,

Huang

Chen

et al. 2022

Ann Transl Med

View full text Add to dashboard Cite

show abstract

“…A T-cell mediated immunity via antigen-specific crosslinking may be implicated ( 29 , 30 ). The ECs regulate key aspects of the immune system, particularly the recruitment and activation of T cells ( 31 , 32 ). Specifically, the ECs can activate effector/memory CD4 and CD8 lymphocytes and promote the expansion of one T cell subtype over another (helper, cytotoxic, or regulatory).…”

Section: Discussionmentioning

confidence: 99%

Endovascular Biopsy of Vertebrobasilar Aneurysm in Patient With Polyarteritis Nodosa

Narsinh

McCoy

et al. 2021

Front. Neurol.

View full text Add to dashboard Cite

Background and Purpose: The management of unruptured intracranial aneurysms remains controversial. The decisions to treat are heavily informed by estimated risk of bleeding. However, these estimates are imprecise, and better methods for stratifying the risk or tailoring treatment strategy are badly needed. Here, we demonstrate an initial proof-of-principle concept for endovascular biopsy to identify the key molecular pathways and gene expression changes associated with aneurysm formation. We couple this technique with single cell RNA sequencing (scRNAseq) to develop a roadmap of the pathogenic changes of a dolichoectatic vertebrobasilar aneurysm in a patient with polyarteritis nodosa.Methods: Endovascular biopsy and fluorescence activated cell sorting was used to isolate the viable endothelial cells (ECs) using the established techniques. A single cell RNA sequencing (scRNAseq) was then performed on 24 aneurysmal ECs and 23 patient-matched non-aneurysmal ECs. An integrated panel of bioinformatic tools was applied to determine the differential gene expression, enriched signaling pathways, and cell subpopulations hypothesized to drive disease pathogenesis.Results: We identify a subset of 7 (29%) aneurysm-specific ECs with a distinct gene expression signature not found in the patient-matched control ECs. A gene set enrichment analysis identified these ECs to have increased the expression of genes regulating the leukocyte-endothelial cell adhesion, major histocompatibility complex (MHC) class I, T cell receptor recycling, tumor necrosis factor alpha (TNFα) response, and interferon gamma signaling. A histopathologic analysis of a different intracranial aneurysm that was later resected yielded a diagnosis of polyarteritis nodosa and positive staining for TNFα.Conclusions: We demonstrate feasibility of applying scRNAseq to the endovascular biopsy samples and identify a subpopulation of ECs associated with cerebral aneurysm in polyarteritis nodosa. Endovascular biopsy may be a safe method for deriving insight into the disease pathogenesis and tailoring the personalized treatment approaches to intracranial aneurysms.

show abstract

“…TECs are known to be particularly important for T cell recruitment and activation. Previous studies have shown that the interaction between T cells and ECs plays an important role in the regulation of the immune system during chronic inflammation ( 106 ). TECs in the tumor microenvironment are particularly relevant to circulating immune cells.…”

Section: The Pro-tumorigenic Effect Of the Relationship Between Strom...mentioning

confidence: 99%

Dual Relationship Between Stromal Cells and Immune Cells in the Tumor Microenvironment

et al. 2022

View full text Add to dashboard Cite

The tumor microenvironment (TME) plays a critical role in tumorigenesis and is comprised of different components, including tumor cells, stromal cells, and immune cells. Among them, the relationship between each mediator involved in the construction of the TME can be understood by focusing on the secreting or expressing factors from each cells. Therefore, understanding the various interactions between each cellular component of the TME is necessary for precise therapeutic approaches. In carcinoma, stromal cells are well known to influence extracellular matrix (ECM) formation and tumor progression through multiple mediators. Immune cells respond to tumor cells by causing cytotoxicity or inflammatory responses. However, they are involved in tumor escape through immunoregulatory mechanisms. In general, anti-cancer therapy has mainly been focused on cancer cells themselves or the interactions between cancer cells and specific cell components. However, cancer cells directly or indirectly influence other TME partners, and members such as stromal cells and immune cells also participate in TME organization through their mutual communication. In this review, we summarized the relationship between stromal cells and immune cells in the TME and discussed the positive and negative relationships from the point of view of tumor development for use in research applications and therapeutic strategies.

show abstract

Endothelial cell and T‐cell crosstalk: Targeting metabolism as a therapeutic approach in chronic inflammation

Cited by 35 publications

References 163 publications

Single-cell transcriptomic analysis revealing changes in retinal cell subpopulation levels and the pathways involved in diabetic retinopathy

Single-cell transcriptomic analysis revealing changes in retinal cell subpopulation levels and the pathways involved in diabetic retinopathy

Endovascular Biopsy of Vertebrobasilar Aneurysm in Patient With Polyarteritis Nodosa

Dual Relationship Between Stromal Cells and Immune Cells in the Tumor Microenvironment

Contact Info

Product

Resources

About