Expression of Notch ligands, Jagged1, 2 and Delta1 in antigen presenting cells in mice

Yamaguchi, Etsuko; Chiba, Shigeru; Kumano, Keiki; Kunisato, Atsushi; Takahashi, Tsuguhiro; Takahashi, Tsuyoshi; Hirai, Hisamaru

doi:10.1016/s0165-2478(01)00326-1

Cited by 77 publications

(52 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moreover, mRNA levels of all four receptor isoforms are increased upon T cell activation implying a potential involvement of more than one Notch isoform [19]. On the other hand APC, in particular DC, express a number of Notch ligands such as Jagged1, Jagged2, Dll1 und Dll4 [16,21]. Generally, all ligands are capable of interacting with all Notch receptors [41][42][43].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Notch ligands Delta-like1, Delta-like4 and Jagged1 differentially regulate activation of peripheral T helper cells

et al. 2005

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

“…Their analysis during APC -T cell interaction is complex since both APC and T cells express various Notch ligands and receptors [12,16,20,21]. Moreover, a number of reports describe an impact of Notch signaling on differentiation and maturation of APC subsets [22][23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Notch ligands Delta-like1, Delta-like4 and Jagged1 differentially regulate activation of peripheral T helper cells

et al. 2005

View full text Add to dashboard Cite

“…23 It is an evolutionarily conserved pathway comprising four Notch ligands (Notch 1-4) and five receptors (Delta-like 1, 3, and 4, Jagged1, and Jagged2). Upon ligand binding, Notch receptors can be split by the g-secretase complex resulting in the release of an active intracellular domain (Notch intracellular domain (NICD)).…”

mentioning

confidence: 99%

Inactivation of Notch signaling reverses the Th17/Treg imbalance in cells from patients with immune thrombocytopenia

Liu

et al. 2015

Laboratory Investigation

View full text Add to dashboard Cite

T helper 17 (Th17) cells and regulatory T (Treg) cells, along with Th1 and Th2 cells, may contribute to the development of immune thrombocytopenia (ITP). The imbalance of Th17/Treg toward Th17 cells has been shown to play a pivotal role in the peripheral immune response. Notch signaling has been implicated in peripheral T-cell activation and effector cell differentiation. However, the role of Th17/Treg in the pathogenesis of ITP and the effect of Notch signaling on Th17/Treg imbalances remain largely elusive in ITP. In vitro, we treated peripheral blood mononuclear cells (PBMCs) from ITP and healthy controls with g-secretase inhibitor (DAPT). Th17 cells and Treg cells were measured by flow cytometry and IL-17, IL-21, and IL-10 secretion by enzyme immunoassay technique. The mRNA expression of Ntoch1, Hes1, Hey1, RORgt, and Foxp3 was investigated by RT-PCR. Cell proliferation and apoptosis were determined by the Cell Counting Kit-8 and apoptosis detection kit. We demonstrated that DAPT was effective in inhibiting mRNA expression of Notch signaling molecules. In untreated cultured PBMCs from ITP patients, we observed elevated Th17 cell and IL-21 levels and RORgt mRNA expression, decreased Treg cells and Foxp3 mRNA expression, and an increased ratio of Th17/Treg and RORgt/Foxp3. After inactivating Notch signal by DAPT, Th17 cells and Th17/Treg ratio were dose dependently decreased and accompanied by the reduction of IL-17 in culture supernatants and RORgt mRNA expression in ITP patients. However, no significant difference was found for Treg cells and Foxp3 mRNA expression, RORgt/Foxp3 ratio, and IL-21 and IL-10 levels after DAPT treatment in ITP patients. We also present evidence that the effect of DAPT inhibition on the Th17 cell response was associated with downregulation of RORgt and IL-17 transcription using human in vitro polarization. In conclusion, our findings highlight the importance of Notch signaling in Th17/Treg imbalances in ITP. Inactivation of Notch signaling might be a potential immunoregulatory strategy in ITP patients.

show abstract

“…T cells also express the Notch ligands Jagged1 (16), Jagged2 (17), and Delta1 (18). Dendritic cells (DCs) express the Notch ligands Jagged1 and Jagged2 as well as Delta4 that are induced by LPS treatment (14,16,17,19). Loss or gain of function strategies have been used to study the role of Notch pathway in T cell maturation.…”

mentioning

confidence: 99%

Jagged1 and Delta1 Differentially Regulate the Outcome of Experimental Autoimmune Encephalomyelitis

Elyaman

Bradshaw

Wang

et al. 2007

The Journal of Immunology

Self Cite

113

View full text Add to dashboard Cite

Notch signaling plays an important role during T cell development in the thymus and in T cell activation but the role of Notch in autoimmunity is not clear. We investigated the role of Jagged1 and Delta1 in experimental autoimmune encephalomyelitis. During experimental autoimmune encephalomyelitis, Delta1 expression is up-regulated on dendritic cells and B cells after priming while Jagged1 is up-regulated only on dendritic cells. Administration of anti-Jagged1 Ab exacerbated clinical disease while that of anti-Delta1 Ab reduced the severity of the clinical disease. In contrast, administration of Jagged1-Fc protected from disease, that of Delta1-Fc exacerbated disease. Treatment with Jagged1-Fc was associated with increased IL-10-producing Ag-specific cells in the CNS, while anti-Jagged1 decreased the frequency of IL-10-producing cells. Treatment with Delta1-Fc increased Th1 cells in the CNS, while anti-Delta-1 decreased the frequency of Th1 cells. Manipulation of Delta1 or Jagged1 had no effect on the frequency of Th17 cells or FoxP3+ cells. Moreover, Jagged1 may play a role in CNS homeostasis because murine astrocytes specifically express Jagged1 that is up-regulated by TGF-β, whereas IFN-γ, TNF-α, and IL-17 decrease Jagged1 expression. Our study provides novel data about differential roles of Notch ligands in regulating inflammation in the periphery as well as in the CNS.

show abstract

Expression of Notch ligands, Jagged1, 2 and Delta1 in antigen presenting cells in mice

Cited by 77 publications

References 19 publications

Notch ligands Delta-like1, Delta-like4 and Jagged1 differentially regulate activation of peripheral T helper cells

Notch ligands Delta-like1, Delta-like4 and Jagged1 differentially regulate activation of peripheral T helper cells

Inactivation of Notch signaling reverses the Th17/Treg imbalance in cells from patients with immune thrombocytopenia

Jagged1 and Delta1 Differentially Regulate the Outcome of Experimental Autoimmune Encephalomyelitis

Contact Info

Product

Resources

About