Regulation of innate and adaptive immunity by Notch

Radtke, Freddy; MacDonald, H. Robson; Tacchini‐Cottier, Fabienne

doi:10.1038/nri3445

Cited by 353 publications

(317 citation statements)

References 122 publications

(132 reference statements)

Supporting

Mentioning

311

Contrasting

Unclassified

Order By: Relevance

“…In the immune system, the Notch signaling pathway has been shown to control the development of multiple cell types, including T cells, marginal zone B cells, innate lymphoid cells, and dendritic cells (DCs) (12). Apart from playing crucial roles for the development of immune cells, the Notch signaling pathway also regulates T cell response.…”

mentioning

confidence: 99%

See 1 more Smart Citation

The Notch Signaling Pathway Controls Short-Lived Effector CD8+ T Cell Differentiation but Is Dispensable for Memory Generation

Mathieu

Duval

Daudelin

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

Following an infection, naive CD8+ T cells expand and differentiate into two main populations of effectors: short-lived effector cells (SLECs) and memory precursor effector cells (MPECs). There is limited understanding of the molecular mechanism and cellular processes governing this cell fate. Notch is a key regulator of cell fate decision relevant in many immunological pathways. In this study, we add to the role of Notch in cell fate decision and demonstrate that the Notch signaling pathway controls the MPEC/SLEC differentiation choice following both Listeria infection and dendritic cell immunization of mice. Although fewer SLECs were generated, Notch deficiency did not alter the rate of memory CD8+ T cell generation. Moreover, we reveal that the Notch signaling pathway plays a context-dependent role for optimal cytokine production by effector CD8+ T cells. Together, our results unravel critical functions for the Notch signaling pathway during effector CD8+ T cell differentiation.

show abstract

mentioning

confidence: 99%

“…Apart from playing crucial roles for the development of immune cells, the Notch signaling pathway also regulates T cell response. Indeed, T cells express Notch receptors, whereas APCs can express the ligands (12). In CD4 + T cells, Notch signaling regulates the differentiation and response of various Th cell subsets (12).…”

mentioning

confidence: 99%

The Notch Signaling Pathway Controls Short-Lived Effector CD8+ T Cell Differentiation but Is Dispensable for Memory Generation

Mathieu

Duval

Daudelin

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Thus, our results revealed a novel role for the Notch-RBP-Jk-IL-7Ra axis that is independent of Hes1 for homeostasis of IL-17 + gd T cells. The Journal of Immunology, 2015, 194: 243-251. N otch signaling plays essential roles in T cell development, such as lineage commitment and maturation, in the thymus (1,2). In mammals, four Notch receptors (Notch1, Notch2, Notch3, and Notch4) are bound to five ligands: D-like (Dll)1, Dll3, Dll4, Jagged1, and Jagged2.…”

mentioning

confidence: 99%

A Genome-Wide Analysis Identifies a Notch–RBP-Jκ–IL-7Rα Axis That Controls IL-17–Producing γδ T Cell Homeostasis in Mice

Nakamura

Shibata

Hatano

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

Notch signaling is an important regulator for the development and function of both αβ and γδ T cells, whereas roles of Notch signaling in T cell maintenance remain unclear. We reported previously that the Notch–Hes1 pathway was involved in the intrathymic development of naturally occurring IL-17–producing (IL-17+) γδ T cells. To gain insight into additional roles for the Notch axis in the homeostasis of γδ T cells, we performed a genome-wide analysis of Notch target genes and identified the novel promoter site of IL-7Rα driven by the Notch–RBP-Jκ pathway. Constitutive Notch signaling had the potential to induce IL-7Rα expression on γδ T cells in vivo, as well as in vitro, whereas conditional deletion of RBP-Jκ abrogated IL-7Rα expression, but not Hes1 expression, by γδ T cells and selectively reduced the pool size of IL-7Rαhigh IL-17+ γδ T cells in the periphery. In the absence of IL-7Rα–mediated signaling, IL-17+ γδ T cells were barely maintained in adult mice. Addition of exogenous IL-7 in vitro selectively expanded IL-17+ γδ T cells. Thus, our results revealed a novel role for the Notch–RBP-Jκ–IL-7Rα axis that is independent of Hes1 for homeostasis of IL-17+ γδ T cells.

show abstract

“…Such Positive correlation should be confirmed with more future studies in both of paediatric and adult ITP as it may be of value in Fig. 1 A comparison between the three studied groups, as regards the median of the expression levels of Notch1 and Hes1, being higher in the newly diagnosed ITP than in the persistent ITP cases and non-ITP controls with high statistical difference (P value \ 0.001, P \ 0.001) respectively using Notch1 and Hes1 as therapeutic target genes in ITP [6,26]. According to our findings, 11/22(50 %) of newly diagnosed ITP and 7/20(35 %) of persistent ITP cases showed very high Hes1 expression levels associated with very low Notch1 expression levels, which may be related to the multiple signal inputs from different pathways such as Sonic Hedgehog, c-Jun-N-terminal kinase and tumor necrosis factor a pathways that control Hes1 expression in different cell types [27][28][29][30][31].…”

Section: Discussionmentioning

confidence: 98%

“…Notch signalling plays an important role in the immune system [6]. It regulates multiple steps of T and B cell development, T cell activation, regulatory T-cell function and T-helper cell differentiation [7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Correlation of Notch1/Hes1 Genes Expression Levels in Egyptian Paediatric Patients with Newly Diagnosed and Persistent Primary Immune(Idiopathic) Thrombocytopenic Purpura

Gawdat

Hammam

Ezzat

2015

Indian J Hematol Blood Transfus

View full text Add to dashboard Cite

Notch signalling is involved in the development of several autoimmune diseases, one of such diseases is ITP. The aim of this study was to investigate and compare the expression levels of Notch1 receptor and its target Hes1 gene in Egyptian paediatric ITP patients. Real-time quantitative reverse transcriptase polymerase chain reaction was used to analyse the expression levels of Notch1 and Hes1 in 42 children with primary ITP (22 newly diagnosed and 20 persistent) cases. Twenty age and sex matched non-ITP controls were included. The expression levels of Notch1 were higher in newly diagnosed and persistent cases than controls with high statistical significant difference (P value \ 0.001, P \ 0.001) respectively, similarly as regards the expression levels of HES1 (P value \ 0.001, P \ 0.007) respectively. A significant positive correlation was found between Notch1 and Hes1 expression levels in newly diagnosed cases (r = 0.587, P value = 0.004). There was an association between levels of both genes in most of ITP patients but Hes1 was markedly elevated than Notch1 in few cases. High expression levels of Notch1/Hes1 indicated the important role of Notch signalling in both newly diagnosed and persistent ITP. High expression levels of Hes1 than Notch1 may shed light on its value as a therapeutic target for future research in ITP.

show abstract

Regulation of innate and adaptive immunity by Notch

Cited by 353 publications

References 122 publications

The Notch Signaling Pathway Controls Short-Lived Effector CD8+ T Cell Differentiation but Is Dispensable for Memory Generation

The Notch Signaling Pathway Controls Short-Lived Effector CD8+ T Cell Differentiation but Is Dispensable for Memory Generation

A Genome-Wide Analysis Identifies a Notch–RBP-Jκ–IL-7Rα Axis That Controls IL-17–Producing γδ T Cell Homeostasis in Mice

Correlation of Notch1/Hes1 Genes Expression Levels in Egyptian Paediatric Patients with Newly Diagnosed and Persistent Primary Immune(Idiopathic) Thrombocytopenic Purpura

Contact Info

Product

Resources

About