scholarly journals NFAT control of innate immunity

Blood ◽  
2012 ◽  
Vol 120 (7) ◽  
pp. 1380-1389 ◽  
Author(s):  
Jan Fric ◽  
Teresa Zelante ◽  
Alicia Y. W. Wong ◽  
Alexandra Mertes ◽  
Hong-Bing Yu ◽  
...  
Keyword(s):  
Innate Immunity ◽  
T Cell ◽  
Myeloid Cells ◽  
Immunosuppressive Drugs ◽  
Molecular Pathways ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Host Protection ◽  
Cell Functions

Abstract The calcineurin/nuclear factor of activated T cells (NFAT) signaling pathway mediates multiple adaptive T-cell functions, but recent studies have shown that calcineurin/NFAT signaling also contributes to innate immunity and regulates the homeostasis of innate cells. Myeloid cells, including granulocytes and dendritic cells, can promote inflammation, regulate adaptive immunity, and are essential mediators of early responses to pathogens. Microbial ligation of pattern-recognition receptors, such as TLR4, CD14, and dectin 1, is now known to induce the activation of calcineurin/NFAT signaling in myeloid cells, a finding that has provided new insights into the molecular pathways that regulate host protection. Inhibitors of calcineurin/NFAT binding, such as cyclosporine A and FK506, are broadly used in organ transplantation and can act as potent immunosuppressive drugs in a variety of different disorders. There is increasing evidence that these agents influence innate responses as well as inhibiting adaptive T-cell functions. This review focuses on the role of calcineurin/NFAT signaling in myeloid cells, which may contribute to the various unexplained effects of immunosuppressive drugs already being used in the clinic.

scholarly journals Human T-Cell Lymphotropic Virus Type 1 p12I Expression Increases Cytoplasmic Calcium To Enhance the Activation of Nuclear Factor of Activated T Cells

2002 ◽  
Vol 76 (20) ◽  
pp. 10374-10382 ◽  
Author(s):  
Wei Ding ◽  
Björn Albrecht ◽  
Robert E. Kelley ◽  
Natarajan Muthusamy ◽  
Seung-Jae Kim ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Calcium Release ◽  
Nuclear Factor ◽  
Cytoplasmic Calcium ◽  
Activated T Cells ◽  
Human T Cell ◽  
Nfat Activation

ABSTRACT Human T-cell lymphotropic virus type 1 (HTLV-1) establishes persistent infection and is associated with lymphoproliferative or neurodegenerative diseases. As a complex retrovirus, HTLV-1 contains typical structural and enzymatic genes, as well as regulatory and accessory genes encoded in the pX region. The early events necessary for HTLV-1 to establish infection in lymphocytes, its primary target cells, remain unresolved. Recent studies have demonstrated the importance of regulatory and accessory gene products in determining this virus-host interaction. Among these, pX open reading frame I, which encodes two proteins, p12I and p27I, is required for establishing persistent infection in vivo and for infection in quiescent primary lymphocytes. In addition, p12I localizes in the endoplasmic reticulum (ER) and cis-Golgi apparatus and associates with a calcium binding protein, calreticulin. We recently reported that p12I expression induces the calcium-responsive T-cell transcription factor, nuclear factor of activated T cells (NFAT), in the presence of phorbol ester activation. Based on these studies, we hypothesize that p12I may modulate calcium release from the ER. Here, we report that p12I expression increases basal cytoplasmic calcium and concurrently diminishes calcium available for release from the ER stores. Overexpression of calreticulin, a calcium buffer protein, blocked p12I-mediated NFAT activation independently of its ability to bind p12I. Chemical inhibition studies using inhibitors of inositol 1,4,5-triphosphate receptor and calcium release-activated calcium channels suggest that inositol 1,4,5-triphosphate receptor in the ER membrane and calcium release-activated calcium channels in the plasma membrane contribute to p12I-mediated NFAT activation. Collectively, our results are the first to demonstrate the role of p12I in elevating cytoplasmic calcium, an antecedent to T-cell activation, and further support the important role of this accessory protein in the early events of HTLV-1 infection.

scholarly journals Signals from OX40 regulate nuclear factor of activated T cells c1 and T cell helper 2 lineage commitment

2006 ◽  
Vol 103 (10) ◽  
pp. 3740-3745 ◽  
Author(s):  
T. So ◽  
J. Song ◽  
K. Sugie ◽  
A. Altman ◽  
M. Croft
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lineage Commitment ◽  
Nuclear Factor ◽  
Activated T Cells

scholarly journals The role of ferroptosis in breast cancer patients: a comprehensive analysis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Zeng-Hong Wu ◽  
Yun Tang ◽  
Hong Yu ◽  
Hua-Dong Li
Keyword(s):  
Breast Cancer ◽  
T Cell ◽  
Signaling Pathway ◽  
Differentially Expressed Genes ◽  
Function Analysis ◽  
Cancer Prognosis ◽  
Differentially Expressed ◽  
Immune Checkpoints ◽  
Cell Functions

AbstractBreast cancer (BC) affects the breast tissue and is the second most common cause of mortalities among women. Ferroptosis is an iron-dependent cell death mode that is characterized by intracellular accumulation of reactive oxygen species (ROS). We constructed a prognostic multigene signature based on ferroptosis-associated differentially expressed genes (DEGs). Moreover, we comprehensively analyzed the role of ferroptosis-associated miRNAs, lncRNAs, and immune responses. A total of 259 ferroptosis-related genes were extracted. KEGG function analysis of these genes revealed that they were mainly enriched in the HIF-1 signaling pathway, NOD-like receptor signaling pathway, central carbon metabolism in cancer, and PPAR signaling pathway. Fifteen differentially expressed genes (ALOX15, ALOX15B, ANO6, BRD4, CISD1, DRD5, FLT3, G6PD, IFNG, NGB, NOS2, PROM2, SLC1A4, SLC38A1, and TP63) were selected as independent prognostic factors for BC patients. Moreover, T cell functions, including the CCR score, immune checkpoint, cytolytic activity, HLA, inflammation promotion, para-inflammation, T cell co-stimulation, T cell co-inhibition, and type II INF responses were significantly different between the low-risk and high-risk groups of the TCGA cohort. Immune checkpoints between the two groups revealed that the expressions of PDCD-1 (PD-1), CTLA4, LAG3, TNFSF4/14, TNFRSF4/8/9/14/18/25, and IDO1/2 among others were significantly different. A total of 1185 ferroptosis-related lncRNAs and 219 ferroptosis-related miRNAs were also included in this study. From the online database, we identified novel ferroptosis-related biomarkers for breast cancer prognosis. The findings of this study provide new insights into the development of new reliable and accurate cancer treatment options.

scholarly journals Role of the Ca2+-Calcineurin-Nuclear Factor of Activated T cell Pathway in Mitofusin-2-Mediated Immune Function of Jurkat Cells

2018 ◽  
Vol 131 (3) ◽  
pp. 330-338 ◽  
Author(s):  
Xiu-Ping Xu ◽  
Yong-Ming Yao ◽  
Guang-Ju Zhao ◽  
Zong-Sheng Wu ◽  
Jun-Cong Li ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Function ◽  
Jurkat Cells ◽  
Nuclear Factor ◽  
Mitofusin 2 ◽  
Activated T Cell

scholarly journals Calcineurin-nuclear factor for activated T cells (NFAT) signaling in pathophysiology of wound healing

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Takahiro Manabe ◽  
Heamin Park ◽  
Takashi Minami
Keyword(s):  
Wound Healing ◽  
Immune Cell ◽  
Repair System ◽  
Nuclear Factor ◽  
Medical Studies ◽  
Activated T Cells ◽  
Mural Cells ◽  
Multiple Organs ◽  
Nfat Activation

AbstractWound healing occurred with serial coordinated processes via coagulation-fibrinolysis, inflammation following to immune-activation, angiogenesis, granulation, and the final re-epithelization. Since the dermis forms critical physical and biological barriers, the repair system should be rapidly and accurately functioned to keep homeostasis in our body. The wound healing is impaired or dysregulated via an inappropriate microenvironment, which is easy to lead to several diseases, including fibrosis in multiple organs and psoriasis. Such a disease led to the dysregulation of several types of cells: immune cells, fibroblasts, mural cells, and endothelial cells. Moreover, recent progress in medical studies uncovers the significant concept. The calcium signaling, typically the following calcineurin-NFAT signaling, essentially regulates not only immune cell activations, but also various healing steps via coagulation, inflammation, and angiogenesis. In this review, we summarize the role of the NFAT activation pathway in wound healing and discuss its overall impact on future therapeutic ways.

scholarly journals Opa+ and Opa− Isolates of Neisseria meningitidis and Neisseria gonorrhoeae Induce Sustained Proliferative Responses in Human CD4+ T Cells

2009 ◽  
Vol 77 (11) ◽  
pp. 5170-5180 ◽  
Author(s):  
Abdel-Rahman Youssef ◽  
Michiel van der Flier ◽  
Silvia Estevão ◽  
Nico G. Hartwig ◽  
Peter van der Ley ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Neisseria Meningitidis ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Activated T Cells ◽  
Bacterial Surface ◽  
Host Immune Responses ◽  
Cell Functions

ABSTRACT T cells may interact with a number of bacterial surface antigens, an encounter which has the potential to downmodulate host immune responses. Neisseria meningitidis, a human colonizer and an agent of septicemia and meningitis, expresses Opa proteins which interact with the CEACAM1 receptor expressed on activated T cells. Since CEACAM1 can act as an inhibitory receptor and T cells in subepithelial tissues may encounter whole bacteria, which often express Opa proteins in vivo, this study assessed primarily if Opa proteins expressed on meningococci affect T-cell functions. In addition, Opa-containing outer membrane vesicles (OMV) have been used as vaccine antigens, and therefore Opa+ and Opa− OMV were also studied. While Opa+ bacteria adhered to CEACAM-expressing T cells, both the Opa+ and Opa− phenotypes induced no to a small transient depression, followed by a prolonged increase in proliferation as well as cytokine production. Such responses were also observed with heat-killed bacteria or OMV. In addition, while anti-CEACAM antibodies alone inhibited proliferation, on coincubation of T cells with bacteria and the antibodies, bacterial effects predominated and were Opa independent. Thus, while Opa proteins of N. meningitidis can bind to T-cell-expressed CEACAM1, this is not sufficient to overcome the T-cell recognition of bacterial factors, which results in a proliferative and cytokine response, an observation consistent with the ability of the host to establish lasting immunity to Opa-expressing meningococci that it frequently encounters. The data also imply that Opa-proficient vaccine preparations may not necessarily inhibit T-cell functions via CEACAM1 binding.

scholarly journals SHP-1 Acts as a Key Regulator of Alloresponses by Modulating LFA-1-Mediated Adhesion in Primary Murine T Cells

2016 ◽  
Vol 36 (24) ◽  
pp. 3113-3127 ◽  
Author(s):  
Martin G. Sauer ◽  
Jessica Herbst ◽  
Ulf Diekmann ◽  
Christopher E. Rudd ◽  
Christian Kardinal
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tyrosine Phosphatase ◽  
Activated T Cells ◽  
Sirna Knockdown ◽  
Antigen Presenting ◽  
Pharmaceutical Agents ◽  
Interfering Rna ◽  
Clinical Potential

The clinical potential of transplantation is often reduced by T cell-mediated alloresponses that cause graft rejection or graft-versus-host disease. Integrin-mediated adhesion between alloreactive T cells and antigen-presenting cells is essential for allorejection. The identity of the signaling events needed for the activation of integrins such as LFA-1 is poorly understood. Here, we identified a novel role of the protein tyrosine phosphatase SHP-1 in the regulation of murine LFA-1-mediated adhesion in an allograft setting. Upon alloactivation, SHP-1 activity is reduced, resulting in an increase in LFA-1 adhesion compared to that for syngeneically activated T cells. The importance of these differential activation properties was further indicated by small interfering RNA (siRNA) knockdown of SHP-1 in syngeneically and allogeneically stimulated T cells. Mechanistically, SHP-1 modulated the binding of SLP-76 to ADAP by dephosphorylation of the YDGI tyrosine motif of ADAP, a known docking site for the Src family kinase Fyn. This novel key role of SHP-1 in the regulation of LFA-1-mediated adhesion may provide a new insight into T cell-mediated alloresponses and may pave the way to the development of new immunosuppressive pharmaceutical agents.

scholarly journals Role of Phosphodiesterase 7 (PDE7) in T Cell Activity. Effects of Selective PDE7 Inhibitors and Dual PDE4/7 Inhibitors on T Cell Functions

2020 ◽  
Vol 21 (17) ◽  
pp. 6118 ◽  
Author(s):  
Marianna Szczypka
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Splice Variants ◽  
Cell Activity ◽  
Cell Functions ◽  
Simultaneous Inhibition ◽  
And Function

Phosphodiesterase 7 (PDE7), a cAMP-specific PDE family, insensitive to rolipram, is present in many immune cells, including T lymphocytes. Two genes of PDE7 have been identified: PDE7A and PDE7B with three or four splice variants, respectively. Both PDE7A and PDE7B are expressed in T cells, and the predominant splice variant in these cells is PDE7A1. PDE7 is one of several PDE families that terminates biological functions of cAMP—a major regulating intracellular factor. However, the precise role of PDE7 in T cell activation and function is still ambiguous. Some authors reported its crucial role in T cell activation, while according to other studies PDE7 activity was not pivotal to T cells. Several studies showed that inhibition of PDE7 by its selective or dual PDE4/7 inhibitors suppresses T cell activity, and consequently T-mediated immune response. Taken together, it seems quite likely that simultaneous inhibition of PDE4 and PDE7 by dual PDE4/7 inhibitors or a combination of selective PDE4 and PDE7 remains the most interesting therapeutic target for the treatment of some immune-related disorders, such as autoimmune diseases, or selected respiratory diseases. An interesting direction of future studies could also be using a combination of selective PDE7 and PDE3 inhibitors.

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