Notch signaling induces lymphoproliferation, T helper cell activation and Th1/Th2 differentiation in leprosy

Dua, Bhavyata; Upadhyay, Rajni; Natrajan, Mohan; Arora, Mamta; Narayanaswamy, Balaji Kithiganahalli; Joshi, Beenu

doi:10.1016/j.imlet.2019.01.003

Cited by 19 publications

(17 citation statements)

References 18 publications

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“…Besides, PGL‐1 activates macrophages and NO release damaging neurons’ axon and leading to demyelination . Beyond those, macrophages activated by M. Leprae trigger T‐cell response, in a STAT‐4/6‐, CREB‐, Jagged1‐ and Notch‐dependent manner . M. Leprae ‐infected Schwann cells produce IL‐12 and NO in a TLR6‐dependent manner, which implies that M. Leprae could evoke neural damage‐mediated immunity .…”

Section: Clinical Relevancementioning

confidence: 99%

Profiling of how nociceptor neurons detect danger – new and old foes

et al. 2019

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The host evolves redundant mechanisms to preserve physiological processing and homeostasis. These functions range from sensing internal and external threats, creating a memory of the insult and generating reflexes, which aim to resolve inflammation. Impairment in such functioning leads to chronic inflammatory diseases. By interacting through a common language of ligands and receptors, the immune and sensory nervous systems work in concert to accomplish such protective functions. Whilst this bidirectional communication helps to protect from danger, it can contribute to disease pathophysiology. Thus, the somatosensory nervous system is anatomically positioned within primary and secondary lymphoid tissues and mucosa to modulate immunity directly. Upstream of this interplay, neurons detect danger, which prompts the release of neuropeptides initiating (i) defensive reflexes (ranging from withdrawal response to coughing) and (ii) chemotaxis, adhesion and local infiltration of immune cells. The resulting outcome of such neuro‐immune interplay is still ill‐defined, but consensual findings start to emerge and support neuropeptides not only as blockers of TH1‐mediated immunity but also as drivers of TH2 immune responses. However, the modalities detected by nociceptors revealed broader than mechanical pressure and temperature sensing and include signals as various as cytokines and pathogens to immunoglobulins and even microRNAs. Along these lines, we aggregated various dorsal root ganglion sensory neuron expression profiling datasets supporting such wide‐ranging sensing capabilities to help identifying new danger detection modalities of these cells. Thus, revealing unexpected aspects of nociceptor neuron biology might prompt the identification of novel drivers of immunity, means to resolve inflammation and strategies to safeguard homeostasis.

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Section: Clinical Relevancementioning

confidence: 99%

Profiling of how nociceptor neurons detect danger – new and old foes

et al. 2019

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“…However, in our study, the activation level of the NOTCH1 signaling pathway did not differ betweenearly and advanced stage patients. Previous studies suggested that NOTCH1 can induce Th2 cell differentiation [17,18]. The NOTCH-Th2 differentiation pathway was upregulated in early stage patients.…”

Section: Discussionmentioning

confidence: 91%

“…6D). Previous studies have suggested that NOTCH1 can induce Th2 cell differentiation [17,18]. Gene signatures were derived from KEGG and are shown in Table S1.…”

Section: Notch1 Mutation In Advanced Stage Samples Reduced Th2 Cell Dmentioning

confidence: 99%

Downregulation of CCL22 and Mutation of NOTCH1 in Tongue Squamous Cell Carcinoma Decreases Th2 Cell Recruitment and Expression to Predict Poor Clinical Outcomes

Li¹,

Liu²,

Zhou³

et al. 2021

Preprint

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Background: Tongue squamous cell carcinoma (TSCC) exhibits a high rate of local recurrence and cervical lymph node metastasis. The effect of the tumor microenvironment on TSCC remains unclear.Methods: Transcriptome data and somatic mutation data of TSCC were obtained from the HNSC project of The Cancer Genome Atlas (TCGA). Immune filtration analysis between early stage (clinical stage I–II) and advanced stage (III–IV) was performed using single-sample Gene Set Enrichment Analysis and MCPcounter. Differentially expressed genes were filtered and their related functions were analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. Kaplan-Meier survival analysis and a Cox-regression model were used to evaluate the survival of patients with the CCL22 signature. Maftools was used to show an overview of somatic mutations in TSCC. Results: In patients with TSCC, Th2 cells were significantly increased in patients in the early stage of the disease. The Th2 cell-related chemokine CCL22 was downregulated in patients in the advanced stage. Univariate and multivariate Cox analyses revealed CCL22 as a good prognostic factor for TSCC. A nomogram based on the expression of CCL22 was constructed as a prognostic indicator for TSCC. NOTCH1 mutation was increased in patients in the advanced stage, which inhibited activation of the NOTCH1-Th2 differentiation pathway.Conclusions: In TSCC, high expression of CCL22 can promote the recruitment of Th2 cells and predict better survival. Mutation of NOTCH1 inhibits the differentiation of Th2 cells. Combined with decreased Th2 cell recruitment and differentiation, tumor progression may occur.

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“…The mRNA expression of Notch1 increased after EAE-specific Ag stimulated peripheral lymphocytes (Jurynczyk et al, 2008). Notch1 expression was higher in Mycobacterium leprae-infected patients than in uninfected controls (Dua et al, 2019). The expression of Notch1 also increased in aplastic anemia (Roderick et al, 2013).…”

Section: Discussionmentioning

confidence: 96%

“…Notch signaling has been considered as a critical regulator for the differentiation and function of immune cells including T cells. There is accumulating evidence that Notch signaling can regulate naive CD4 + T-cell differentiation into the Th1 type (Maekawa et al, 2003;Minter et al, 2005;Skokos and Nussenzweig, 2007;Zhang et al, 2011;Roderick et al, 2013;Amsen et al, 2015;Verma et al, 2016;Dua et al, 2019). Studies using preclinical models have also revealed the potential therapy of targeting Notch signaling to reduce immune pathology, highlighting the mechanism by which Notch signaling regulates the differentiation and function of T cell (Amsen et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

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

Xie

Wen

Chen

et al. 2020

Front. Cell. Infect. Microbiol.

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Helicobacter pylori infection induces CD4 + T differentiation cells into IFN-γ-producing Th1 cells. However, the details of mechanism underlying this process remain unclear. Notch signal pathway has been reported to regulate the differentiation of CD4 + T cells into Th1 subtype in many Th1-mediated inflammatory disorders but not yet in H. pylori infection. In the present study, the mRNA expression pattern of CD4 + T cells in H. pylori-infected patients differed from that of healthy control using Human Signal Transduction Pathway Finder RT2 Profiler PCR Array, and this alteration was associated with Notch signal pathway, as analyzed by Bioinformation. Quantitative real-time PCR showed that the mRNA expression of Notch1 and its target gene Hes-1 in CD4 + T cells of H. pylori-infected individuals increased compared with the healthy controls. In addition, the mRNA expression of Th1 master transcription factor T-bet and Th1 signature cytokine IFN-γ was both upregulated in H. pylori-infected individuals and positively correlated with Notch1 expression. The increased protein level of Notch1 and IFN-γ were also observed in H. pylori-infected individuals confirmed by flow cytometry and ELISA. In vitro, inhibition of Notch signaling decreased the mRNA expression of Notch1, Hes-1, T-bet, and IFN-γ, and reduced the protein levels of Notch1 and IFN-γ and the secretion of IFN-γ in CD4 + T cells stimulated by H. pylori. Collectively, this is the first evidence that Notch1 is upregulated and involved in the differentiation of Th1 cells during H. pylori infection, which will facilitate exploiting Notch1 as a therapeutic target for the control of H. pylori infection.

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Notch signaling induces lymphoproliferation, T helper cell activation and Th1/Th2 differentiation in leprosy

Cited by 19 publications

References 18 publications

Profiling of how nociceptor neurons detect danger – new and old foes

Profiling of how nociceptor neurons detect danger – new and old foes

Downregulation of CCL22 and Mutation of NOTCH1 in Tongue Squamous Cell Carcinoma Decreases Th2 Cell Recruitment and Expression to Predict Poor Clinical Outcomes

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

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