Notch signalling suppresses regulatory T‐cell function in murine experimental autoimmune uveitis

Hua, Rong; Shen, Hongjie; Xu, Yue-Li; Hai, Yang

doi:10.1111/imm.12663

Cited by 19 publications

(16 citation statements)

References 40 publications

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“…In vitro signaling with recombinant Dll4 protein inhibited TGF-b-dependent induction of T regs and activation of STAT5, a transcription factor implicated in Foxp3 expression [55]. Similar results were obtained in experimental autoimmune uveitis, where the down-regulation of Notch signaling in infiltrating T regs increased their immunosuppressive function [56]. Overall, these results underline, once again, the crucial impact of the receptor/ligand pair type in determining the outcomes of Notch, especially in pathologic settings.…”

Section: Notch and Pt Regs /It Regssupporting

confidence: 64%

The mazy case of Notch and immunoregulatory cells

Grazioli

Felli

Screpanti

et al. 2017

Journal of Leukocyte Biology

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The Notch pathway represents a conserved signal transduction machinery that is straightforward and based on a few elements (ligands, receptors, transducers). However, the existence of multiple control levels of the Notch signaling final outcome makes it strictly context dependent and dose dependent. The function of Notch as a regulator of cell development and differentiation, as well as the aberrant consequences of its modulation, either positive or negative, is well established. In this review, we will discuss our current knowledge about Notch-dependent regulation of generation and function of 2 subsets of the immunoregulatory system, namely regulatory T cells (T) and myeloid-derived suppressor cells (MDSCs). Then, we will focus on an unforeseen mechanism that may unveil an additional way of Notch to govern the surrounding environment in cancer.

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Section: Notch and Pt Regs /It Regssupporting

confidence: 64%

The mazy case of Notch and immunoregulatory cells

Grazioli

Felli

Screpanti

et al. 2017

Journal of Leukocyte Biology

View full text Add to dashboard Cite

show abstract

“…In this study, we isolated and cultured CD4 + T cells from PV patients; consistent with findings from ITP and hepatitis C patients, after DAPT treatment, no significant difference was found in expression levels of Treg cells, its specific transcription factor, and effective cytokine. Hence, the influence of Notch1 signaling on Treg cells and the response of Treg cells to Notch inactivation may depend on distinct experimental systems and diseases [ 41 ], and this needs to be clarified in the future.…”

Section: Discussionmentioning

confidence: 99%

Notch1 Signaling Regulates the Th17/Treg Immune Imbalance in Patients with Psoriasis Vulgaris

Xue

Gao

et al. 2018

Mediators of Inflammation

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Purpose To evaluate the regulating effect of Notch1 signaling on Th17/Treg immune imbalance in psoriasis vulgaris (PV). Materials and Methods Notch1, Hes-1, RORγt, Foxp3, IL-17, and IL-10 mRNA expression, as well as Th17 and Treg cell percentages in peripheral CD4+ T cells, were detected by real-time quantitative RT-PCR and flow cytometry, and serum concentrations of IL-17 and IL-10 were detected by ELISA in 36 PV patients and 32 healthy controls. Additionally, CD4+ T cells from 12 PV patients were treated with γ-secretase inhibitor DAPT, and the above indexes were measured. Results PV patients presented distinct Th17/Treg immune imbalance and highly expressed Notch1 and Hes-1 mRNA levels, which were positively correlated with psoriasis area and severity index (PASI) and the ratios of Th17/Treg and RORγt/Foxp3. DAPT treatment resulted in the obvious downregulation of Th17 cell percentage in cocultured CD4+ T cells, RORγt and IL-17 mRNA levels, and IL-17 concentration in cell-free supernatant from cocultured CD4+ T cells of PV patients in a dose-dependent manner, while there was no significant influence on Treg cell percentage, Foxp3, and IL-10 expression, therefore leading to the recovery of Th17/Treg immune imbalance. Conclusion Notch1 signaling may contribute to the pathogenesis of PV by regulating Th17/Treg immune imbalance.

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“…Conversely, antibodies against Jagged1 and Dll1 rescued Foxp3 levels. Importantly, transplantation of Tregs with Notch1 deficiency resulted in an increase in the release of inflammatory cytokines and in cellular infiltration in the uveitic eyes (120).…”

Section: Functional Phenotypes Of T-cells Determine Atherosclerosis Pmentioning

confidence: 99%

Notch Signaling Regulates Immune Responses in Atherosclerosis

et al. 2019

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Atherosclerosis is a chronic autoimmune inflammatory disease that can cause coronary artery disease, stroke, peripheral artery disease, depending on which arteries are affected. At the beginning of atherosclerosis plasma lipoproteins accumulate in the sub-endothelial space. In response, monocytes migrate from the circulation through the endothelium into the intima where they differentiate into macrophages. These early events trigger a complex immune response that eventually involves many cellular subtypes of both innate and adaptive immunity. The Notch signaling pathway is an evolutionary conserved cell signaling system that mediates cell-to-cell communication. Recent studies have revealed that Notch modulate atherosclerosis by controlling macrophages polarization into M1 or M2 subtypes. Furthermore, it is known that Notch signaling controls differentiation and activity of T-helper and cytotoxic T-cells in inflammatory diseases. In this review, we will discuss the role of Notch in modulating immunity in the context of atherosclerosis and whether targeting Notch may represent a therapeutic strategy.

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Notch signalling suppresses regulatory T‐cell function in murine experimental autoimmune uveitis

Cited by 19 publications

References 40 publications

The mazy case of Notch and immunoregulatory cells

The mazy case of Notch and immunoregulatory cells

Notch1 Signaling Regulates the Th17/Treg Immune Imbalance in Patients with Psoriasis Vulgaris

Notch Signaling Regulates Immune Responses in Atherosclerosis

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