Notch 1 Is Involved in CD4+ T Cell Differentiation Into Th1 Subtype During Helicobacter pylori Infection

Xie, Jinling; Wen, Junjie; Chen, Chuxi; Luo, Meiqun; Hu, Bingxin; Wu, Danlin; Ye, Jianbin; Lin, Yanqing; Ning, Lijun; Ning, Yuping; Yan, Li

doi:10.3389/fcimb.2020.575271

Cited by 10 publications

(10 citation statements)

References 63 publications

(96 reference statements)

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“…This observation reveals a new mechanism that miR-126a-5p enhances Notch1 signal by targeting delta-like 1 homolog (DLK1) and then promotes the differentiation of CD4 + T cells toward Th1. As a highly conserved signal pathway, Notch is still controversial in regulating CD4 + T-cell differentiation (27)(28)(29)(30)(31), but our results show that Notch1 can regulate CD4 + T-cell differentiation toward Th1.…”

Section: Introductionmentioning

confidence: 61%

“…The Notch1 signaling pathway is controversial in the polarization of Th1/Th2 cell subtypes. On the one hand, Notch1 promotes Th1 subtype differentiation during Helicobacter pylori infection ( 29 ). Taxifolin reduces the proportion of Th1 cells by inhibiting the Notch1 signaling pathway ( 55 ).…”

Section: Discussionmentioning

confidence: 99%

“…DLK1, as a homolog of the ligand DLL, competitively binds to the Notch1 receptor to affect the Notch1 signaling pathway (34)(35)(36). Alternatively, accumulated evidence indicates that Notch1 signaling pathway was involved in CD4 + T-cell differentiation into the Th1 subtype (29,37,38). We then examined the effect of miR-126a-5p on the Notch1 signaling pathway in naive CD4 + T cells.…”

Section: Mir-126a-5p Regulates the Notch1 Signaling Pathway By Target...mentioning

confidence: 99%

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The Recombinant Eg.P29-Mediated miR-126a-5p Promotes the Differentiation of Mouse Naive CD4+ T Cells via DLK1-Mediated Notch1 Signal Pathway

Zhu

Zhang

et al. 2022

Front. Immunol.

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Cystic echinococcosis (CE) is a zoonotic parasitic disease spread worldwide caused by Echinococcus granulosus (Eg), which sometimes causes serious damage; however, in many cases, people are not aware that they are infected. A number of recombinant vaccines based on Eg are used to evaluate their effectiveness against the infection. Our previous report showed that recombinant Eg.P29 (rEg.P29) has a marvelous immunoprotection and can induce Th1 immune response. Furthermore, data of miRNA microarray in mice spleen CD4+ T cells showed that miR-126a-5p was significantly elevated 1 week after immunization by using rEg.P29. Therefore, in this perspective, we discussed the role of miR-126a-5p in the differentiation of naive CD4+ T cells into Th1/Th2 under rEg.P29 immunization and determined the mechanisms associated with delta-like 1 homolog (DLK1) and Notch1 signaling pathway. One week after P29 immunization of mice, we found that miR-126a-5p was significantly increased and DLK1 expression was decreased, while Notch1 pathway activation was enhanced and Th1 response was significantly stronger. The identical conclusion was obtained by overexpression of mmu-miR-126a-5p in primary naive CD4+ T cells in mice. Intriguingly, mmu-miR-126a-5p was significantly raised in serum from mice infected with protoscolex in the early stages of infection and markedly declined in the late stages of infection, while has-miR-126-5p expression was dramatically reduced in serum from CE patients. Taken together, we show that miR-126a-5p functions as a positive regulator of Notch1-mediated differentiation of CD4+ T cells into Th1 through downregulating DLK1 in vivo and in vitro. Hsa-miR-126-5p is potentially a very promising diagnostic biomarker for CE.

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Section: Introductionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Section: Mir-126a-5p Regulates the Notch1 Signaling Pathway By Target...mentioning

confidence: 99%

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The Recombinant Eg.P29-Mediated miR-126a-5p Promotes the Differentiation of Mouse Naive CD4+ T Cells via DLK1-Mediated Notch1 Signal Pathway

Zhu

Zhang

et al. 2022

Front. Immunol.

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“…The expression of Notch ligands in macrophages was induced by dengue virus, which is vital for Th1/Th2 differentiation during adaptive immune response ( Li et al, 2015 ). Our research team previously determined that Notch 1 is involved in the differentiation of Th1 cells in H. pylori patients ( Xie et al, 2020 ). In our next investigation, we will explore how Jagged1 in macrophages interacts with Notch signaling receptors to affect Th1 cell response during H. pylori infection.…”

Section: Discussionmentioning

confidence: 99%

Notch Signaling Ligand Jagged1 Enhances Macrophage-Mediated Response to Helicobacter pylori

et al. 2021

Self Cite

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Helicobacter pylori (H. pylori) is one of the gram-negative bacteria that mainly colonize the stomach mucosa and cause many gastrointestinal diseases, such as gastritis, peptic ulcer, and gastric cancer. Macrophages play a key role in eradicating H. pylori. Recent data have shown that Notch signaling could modulate the activation and bactericidal activities of macrophages. However, the role of Notch signaling in macrophages against H. pylori remains unclear. In the present study, in the co-culture model of macrophages with H. pylori, the inhibition of Notch signaling using γ-secretase decreased the expression of inducible nitric oxide synthase (iNOS) and its product, nitric oxide (NO), and downregulated the secretion of pro-inflammatory cytokine and attenuated phagocytosis and bactericidal activities of macrophages to H. pylori. Furthermore, we identified that Jagged1, one of Notch signaling ligands, was both upregulated in mRNA and protein level in activated macrophages induced by H. pylori. Clinical specimens showed that the number of Jagged1+ macrophages in the stomach mucosa from H. pylori-infected patients was significantly higher than that in healthy control. The overexpression of Jagged1 promoted bactericidal activities of macrophages against H. pylori and siRNA-Jagged1 presented the opposite effect. Besides, the addition of exogenous rJagged1 facilitated the pro-inflammatory mediators of macrophages against H. pylori, but the treatment of anti-Jagged1 neutralizing antibody attenuated it. Taken together, these results suggest that Jagged1 is a promoting molecule for macrophages against H. pylori, which will provide insight for exploring Jagged1 as a novel therapeutic target for the control of H. pylori infection.

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“…The cells were further stimulated with PMA (50ng/ml, Sigma-Aldrich), ionomycin (1μg/ml, Sigma-Aldrich) and 0.4μL BD GolgiStop TM Protein Transport Inhibitor (BD Biosciences) for 5 hours and then stained intracellularly with FITC-conjugated anti-human IFN-γ and PE-conjugated anti-human IL-4 (Biolegend) antibodies. 18 RNA sequencing and functional annotation analyses MDSCs from AA patients and HDs were isolated as described before. Both RNA extraction and sequencing were undertaken at Novogene Inc, as previously reported.…”

Section: Th1 Cells Induction In Vitromentioning

confidence: 99%

Impaired immunosuppressive role of myeloid-derived suppressor cells in acquired aplastic anemia

Dong

Chen

et al. 2022

haematol

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Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous immature myeloid cells and display immunosuppressive function. In this study, MDSCs populations were evaluated in acquired aplastic anemia (AA) (n=65) in which aberrant immune mechanisms contributed to bone marrow destruction. Our data demonstrate that both the proportion and immunosuppressive function of MDSCs are impaired in AA patients. Decreased percentage of MDSCs, especially monocytic-MDSCs, in the blood of AA patients (n=15) is positively correlated with the frequency of T regulatory cells, bone marrow level of WT1 and decreased plasma level of arginase-1. RNA sequence analyses reveal that multiple pathways including DNA damage, interleukin (IL)-4, apoptosis, and Janus kinase (JAK)-signal transducer and activator of transcription (STAT) are upregulated, whereas transcription, IL-6, IL-18, glycolysis, transforming growth factor and reactive oxygen species are downregulated in MDSCs of AA (n=4), compared with that of healthy donors (n=3). These data suggest that AA MDSCs are defective. Administration of rapamycin significantly increases the absolute number of MDSCs and levels of intracellular enzymes, including arginase-1 and inducible nitric-oxide synthase. Moreover, rapamycin inhibits MDSCs from differentiating into mature myeloid cells. These findings reveal that impaired MDSCs are involved in the immunopathogenesis of AA. Pharmacologically targeting of MDSCs by rapamycin might provide a promising therapeutic strategy for AA.

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Notch 1 Is Involved in CD4+ T Cell Differentiation Into Th1 Subtype During Helicobacter pylori Infection

Cited by 10 publications

References 63 publications

The Recombinant Eg.P29-Mediated miR-126a-5p Promotes the Differentiation of Mouse Naive CD4+ T Cells via DLK1-Mediated Notch1 Signal Pathway

The Recombinant Eg.P29-Mediated miR-126a-5p Promotes the Differentiation of Mouse Naive CD4+ T Cells via DLK1-Mediated Notch1 Signal Pathway

Notch Signaling Ligand Jagged1 Enhances Macrophage-Mediated Response to Helicobacter pylori

Impaired immunosuppressive role of myeloid-derived suppressor cells in acquired aplastic anemia

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