Immunomodulatory effect of tea saponin in immune T-cells and T-lymphoma cellsviaregulation of Th1, Th2 immune response and MAPK/ERK2 signaling pathway

Abstract Background: Pancreatic cancer (PC) is a highly lethal disease and an increasing cause of cancer-associated mortality worldwide. Interferon regulatory factors (IRFs) play vital roles in immune response and tumor cellular biological process. However, the specific functions of IRFs in PC and tumor immune response are far from systematically clarified. This study aimed to explorer the expression profile, prognostic significance, and biological function of IRFs in PC.Results: We observed that the level of IRF3, 6, 7, 8, and 9 were elevated in tumor compared to normal tissues in PC. IRF7 expression was significantly associated with patients’ pathology stage in PC. PC patients with high IRF2, low IRF3, and high IRF6 level had significantly poorer overall survival. High mRNA expression, amplification and deep deletion were the three most common types of genetic alterations of IRFs in PC. Low expression of IRF2, 4, 5, and 8 was resistant to most of the drugs or small molecules from Genomics of Drug Sensitivity in Cancer. Moreover, IRFs were positively correlated with the abundance of tumor infiltrating immune cells in PC, including B cells, CD8+ T cells, CD4+ T cells, macrophages, Neutrophil, and Dendritic cells. Functional analysis indicated that IRFs were involved in T cell receptor signaling pathway, immune response and Toll-like receptor signaling pathway. Conclusions: Our results indicated that certain IRFs could serve as potential therapeutic targets and prognostic biomarker for PC patients. Further basic and clinical studies are needed to validate our findings and generalize the clinical application of IRFs in PC.

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Vaccination with Trichinella Spirallis Antigens Increases CD8+ Peripheral T Cells and Enhances the TH2 Immune Response in Leishmania Infantum Challenged MICE

International Journal of Immunopathology and Pharmacology ◽

10.1177/039463200902200119 ◽

2009 ◽

Vol 22 (1) ◽

pp. 169-174 ◽

Cited By ~ 2

Author(s):

M. Daoudaki ◽

A. Diakou ◽

S. Frydas ◽

I. Fouzas ◽

E. Karagounp ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Leishmania Infantum ◽

Th2 Immune Response ◽

Peripheral T Cells

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Aspirin Attenuates Cardiac Allograft Rejection by Inhibiting the Maturation of Dendritic Cells via the NF-κB Signaling Pathway

Frontiers in Pharmacology ◽

10.3389/fphar.2021.706748 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xi Zhang ◽

Aie Chang ◽

Yanqiang Zou ◽

Heng Xu ◽

Jikai Cui ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Dendritic Cells ◽

Signaling Pathway ◽

Inflammatory Cytokines ◽

Allograft Rejection ◽

Cardiac Allograft ◽

Cardiac Allograft Rejection ◽

Pro Inflammatory Cytokines

Background: Dendritic cells (DCs) serve as an important part of the immune system and play a dual role in immune response. Mature DCs can initiate immune response, while immature or semi-mature DCs induce immune hyporesponsiveness or tolerance. Previous studies have shown that aspirin can effectively inhibit the maturation of DCs. However, the protective effect of aspirin on acute cardiac allograft rejection has not been studied. The aim of this study was to elucidate the effect of aspirin exert on allograft rejection.Methods: The model of MHC-mismatched (BALB/c to B6 mice) heterotopic heart transplantation was established and administered intraperitoneal injection with aspirin. The severity of allograft rejection, transcriptional levels of cytokines, and characteristics of immune cells were assessed. Bone marrow-derived dendritic cells (BMDCs) were generated with or without aspirin. The function of DCs was determined via mixed lymphocyte reaction (MLR). The signaling pathway of DCs was detected by Western blotting.Results: Aspirin significantly prolonged the survival of cardiac allograft in mouse, inhibited the production of pro-inflammatory cytokines and the differentiation of effector T cells (Th1 and Th17), as well as promoted the regulatory T cells (Treg). The maturation of DCs in the spleen was obviously suppressed with aspirin treatment. In vitro, aspirin decreased the activation of NF-κB signaling of DCs, as well as impeded MHCII and co-stimulatory molecules (CD80, CD86, and CD40) expression on DCs. Moreover, both the pro-inflammatory cytokines and function of DCs were suppressed by aspirin.Conclusion: Aspirin inhibits the maturation of DCs through the NF-κB signaling pathway and attenuates acute cardiac allograft rejection.

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TLR2 Agonist Enhances CD8+Foxp3+ Regulatory T cells and Limits Th2 Immune Response during Allergen Immunotherapy

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2010.12.1042 ◽

2011 ◽

Vol 127 (2) ◽

pp. AB262-AB262

Author(s):

C. Lin

Keyword(s):

Immune Response ◽

T Cells ◽

Regulatory T Cells ◽

Allergen Immunotherapy ◽

Tlr2 Agonist ◽

Th2 Immune Response

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HIV-1 and HIV-2 differentially regulate NF-κB activity during the late stages of the replication cycle through BST-2/tetherin antagonism

10.1101/2020.05.11.088385 ◽

2020 ◽

Author(s):

François E. Dufrasne ◽

Géraldine Dessilly ◽

Mara Lucchetti ◽

Kate Soumillion ◽

Eléonore Ngyuvula ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Viral Replication ◽

Signaling Pathway ◽

Replication Cycle ◽

Immune Control ◽

Antiviral Immune Response ◽

Late Stages ◽

Hiv 1 ◽

Tetherin Antagonism

ABSTRACTHIV-2 is the second causative agent of AIDS and is commonly considered as an attenuated form of retroviral infection. Most of HIV-2-infected individuals display a slow-progressing disease, lower viral loads and a stronger immunological control of viral infection as compared with HIV-1-infected patients. The main hypothesis that could explain the difference of disease progression between HIV-1 and HIV-2 implies a more efficient T cell–mediated immunity in the control of HIV-2 infection. Herein, we investigate the effects of the HIV-2 envelope glycoprotein (Env) and its antitetherin function in the NF-κB signaling pathway during single-round infection of CD4+ T cells. First, we report an essential role of the Env cytoplasmic tail (CT) in the activation of this signaling pathway and we also demonstrate that the HIV-2 Env CT activates NF-κB in a TRAF6-dependent but TAK1-independent manner. Further, we show that HIV-2 reference strains and clinical isolates are unable to completely inhibit NF-κB mainly via the Env-mediated BST-2/tetherin antagonism in the late stages of the viral replication cycle in CD4+ T cells, in striking contrast to the HIV-1 Vpu-mediated counteraction of tetherin. We observe that this inability of HIV-2 to suppress NF-κB signaling pathway promotes stimulation of numerous genes involved in the antiviral immune response, such as il-6, il-21 and ifn-β genes. Therefore, HIV-1 and HIV-2 differentially regulate the NF-κB-induced antiviral immune response mainly through the BST-2/tetherin antagonism. These new insights highlight molecular mechanisms determining, at least partly, the distinct immune control and disease outcomes of HIV-1 and HIV-2 infections.IMPORTANCEThis study explores how HIV-1 and HIV-2 diverge in their regulation of the NF-κB signaling pathway. We revealed that HIV-2 fails to completely inhibit NF-κB activity, thereby inducing a stronger antiviral response than HIV-1. We demonstrated that the ability to antagonize the cellular restriction factor BST-2/tetherin largely governs the regulation of the NF-κB pathway: at the late stages of the viral replication cycle, HIV-1 Vpu blocks this pathway whereas HIV-2 Env does not. We also demonstrated that several NF-κB-targeted genes are upregulated in CD4+ T cells infected with HIV-2, but not with HIV-1. This stronger NF-κB-induced antiviral response may explain the better immune control of HIV-2 infection and the differences between HIV-1 and HIV-2 pathogenesis. Moreover, we observed in this study that non-pathogenic isolates of HIV-2 have an impaired NF-κB inhibitory capacity compared to pathogenic ones.

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