Transcription factors STAT-4, STAT-6 and CREB regulate Th1/Th2 response in leprosy patients: effect of M. leprae antigens

Upadhyay, Rajni; Dua, Bhavyata; Sharma, Bhawna; Natrajan, Mohan; Jain, Ashay; Narayanaswamy, Balaji Kithiganahalli; Joshi, Beenu

doi:10.1186/s12879-018-3601-z

Cited by 14 publications

(10 citation statements)

References 29 publications

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“…It is a key component of IL‐12/STAT4/INF‐γ signal transduction pathways in various immune regulatory cells, which is essential for the development of Th1 cells with complete functions . The STAT4 pathway is the main signal transduction pathway for cytokine regulation of immune cell differentiation to Th1 . STAT4‐deficient mice showed an advantage in Th2 immune response .…”

Section: Discussionmentioning

confidence: 99%

The diagnosis values of serum STAT4 and sEng in preeclampsia

Zhang¹,

Li²,

Zhou³

et al. 2019

Clinical Laboratory Analysis

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Objective To detect the levels of signal transducer and activator of transcription 4 (STAT4) and soluble endoglin (sEng) in preeclampsia patients and analyze the diagnostic values of STAT4 and sEng in preeclampsia. Methods Fifty‐four pregnant women with preeclampsia from October 2017 to June 2018 were included in this study. Twenty‐eight matched healthy pregnant women were set as the control group. The general clinical characteristics were measured. Serum STAT4 and sEng were detected by ELISA. Correlation between STAT4 and sEng, and their diagnostic value in preeclampsia were analyzed. Results Compared with control, the prothrombin time in preeclampsia was significantly lower, while the mean arterial pressure, 24‐hour urine protein, serum creatinine, fibrinogen, and ALT were significantly higher. The circulating levels of STAT4 and sEng were significantly increased in the preeclampsia. The serum levels of STAT4 and sEng in preeclampsia were positively correlated. For the diagnosis of preeclampsia by the serum STAT4, AUC is 0.902, and the sensitivity and specificity are 0.893 and 0.929. By the serum sEng, AUC is 0.873, and the sensitivity and specificity are 0.816 and 0.905. Conclusion The serum levels of STAT4 and sEng were significantly increased in preeclampsia with disease severity status, which have promise as diagnostic markers in preeclampsia.

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Section: Discussionmentioning

confidence: 99%

The diagnosis values of serum STAT4 and sEng in preeclampsia

Zhang¹,

Li²,

Zhou³

et al. 2019

Clinical Laboratory Analysis

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show abstract

“…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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“…As seen in the bubble diagram shown in Figure 2B , LA was found to regulate the interleukin (IL)-17 signaling pathway, which is important in immune system function [ 21 , 22 ]. Furthermore, as seen in the heatmap of differentially expressed genes related to the IL-17 signaling pathway, 11 of the detected genes are related to the proliferation of lymphocytes, including T cells, B cells, and NK cells ( Figure 2C and Table 1 ) [ 23 – 45 ]. The RNA-seq analysis results suggest that LA treatment affects the proliferation of lymphocytes, including T cells and B cells, by regulating the IL-17 signaling pathway.…”

Section: Resultsmentioning

confidence: 99%

Licochalcone A improves the cognitive ability of mice by regulating T- and B-cell proliferation

Zhu

Liu³

et al. 2021

Aging

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Licochalcone A (LA), a flavonoid found in licorice, has anticancer, antioxidant, anti-inflammatory, and neuroprotective properties. Here, we explored the effect of injecting LA into the tail vein of middle-aged C57BL/6 mice on their cognitive ability as measured by the Morris water maze (MWM) test and cerebral blood flow (CBF). The related mechanisms were assessed via RNA-seq, and T (CD3e + ) and B (CD45R/B220 + ) cells in the spleen and whole blood were quantified via flow cytometry. LA improved the cognitive ability, according to the MWM test results, and upregulated the CBF level of treated mice. The RNA-seq results indicate that LA affected the interleukin (IL)-17 signaling pathway, which is related to T- and B-cell proliferation, and the flow cytometry data suggest that LA promoted T- and B-cell proliferation in the spleen and whole blood. We also performed immune reconstruction via a tail vein injection of lymphocytes into B-NDG (NOD- Prkdc scid Il2rg tm1 /Bcge) mice before treating them with LA. We tested cognitive ability by subjecting these animals to new object recognition tests and quantified the splenic and whole blood T and B cells. Cognitive ability improved after immune reconstruction and LA treatment, and LA promoted T- and B-cell proliferation in the spleen and whole blood. This study demonstrates that LA, by activating the IL-17 signaling pathway, promotes T- and B-cell proliferation in the spleen and whole blood of mice and improves cognitive ability. Thus, LA may have immune-modulating therapeutic potential for improving cognition.

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Transcription factors STAT-4, STAT-6 and CREB regulate Th1/Th2 response in leprosy patients: effect of M. leprae antigens

Cited by 14 publications

References 29 publications

The diagnosis values of serum STAT4 and sEng in preeclampsia

The diagnosis values of serum STAT4 and sEng in preeclampsia

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

Licochalcone A improves the cognitive ability of mice by regulating T- and B-cell proliferation

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