scholarly journals Blockade of interleukin-27 signaling reduces GVHD in mice by augmenting Treg reconstitution and stabilizing Foxp3 expression

Blood ◽  
2016 ◽  
Vol 128 (16) ◽  
pp. 2068-2082 ◽  
Author(s):  
Ludovic Belle ◽  
Kimberle Agle ◽  
Vivian Zhou ◽  
Cheng Yin-Yuan ◽  
Richard Komorowski ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Regulatory T Cells ◽  
Foxp3 Expression ◽  
Interleukin 27 ◽  
Key Points ◽  
The Stability

Key Points Blockade of IL-27 signaling mitigates the severity of GVHD by recalibrating the effector and regulatory arms of the immune system. Inhibition of IL-27 augments the reconstitution of CD4+ and CD8+ regulatory T cells and increases the stability of Foxp3 expression.

scholarly journals Secretome screening reveals immunomodulating functions of IFNα-7, PAP and GDF-7 on regulatory T-cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mei Ding ◽  
Rajneesh Malhotra ◽  
Tomas Ottosson ◽  
Magnus Lundqvist ◽  
Aman Mebrahtu ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Cell Function ◽  
Foxp3 Expression ◽  
Treg Cells ◽  
Secreted Proteins ◽  
External Stimulation ◽  
Marker Proteins ◽  
Positive Regulators ◽  
Conformational Model

AbstractRegulatory T cells (Tregs) are the key cells regulating peripheral autoreactive T lymphocytes. Tregs exert their function by suppressing effector T cells. Tregs have been shown to play essential roles in the control of a variety of physiological and pathological immune responses. However, Tregs are unstable and can lose the expression of FOXP3 and suppressive functions as a consequence of outer stimuli. Available literature suggests that secreted proteins regulate Treg functional states, such as differentiation, proliferation and suppressive function. Identification of secreted proteins that affect Treg cell function are highly interesting for both therapeutic and diagnostic purposes in either hyperactive or immunosuppressed populations. Here, we report a phenotypic screening of a human secretome library in human Treg cells utilising a high throughput flow cytometry technology. Screening a library of 575 secreted proteins allowed us to identify proteins stabilising or destabilising the Treg phenotype as suggested by changes in expression of Treg marker proteins FOXP3 and/or CTLA4. Four proteins including GDF-7, IL-10, PAP and IFNα-7 were identified as positive regulators that increased FOXP3 and/or CTLA4 expression. PAP is a phosphatase. A catalytic-dead version of the protein did not induce an increase in FOXP3 expression. Ten interferon proteins were identified as negative regulators that reduced the expression of both CTLA4 and FOXP3, without affecting cell viability. A transcriptomics analysis supported the differential effect on Tregs of IFNα-7 versus other IFNα proteins, indicating differences in JAK/STAT signaling. A conformational model experiment confirmed a tenfold reduction in IFNAR-mediated ISG transcription for IFNα-7 compared to IFNα-10. This further strengthened the theory of a shift in downstream messaging upon external stimulation. As a summary, we have identified four positive regulators of FOXP3 and/or CTLA4 expression. Further exploration of these Treg modulators and their method of action has the potential to aid the discovery of novel therapies for both autoimmune and infectious diseases as well as for cancer.

scholarly journals SENP3 maintains the stability and function of regulatory T cells via BACH2 deSUMOylation

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Xiaoyan Yu ◽  
Yimin Lao ◽  
Xiao-Lu Teng ◽  
Song Li ◽  
Yan Zhou ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
The Stability ◽  
And Function

scholarly journals Autologous stem cell transplantation aids autoimmune patients by functional renewal and TCR diversification of regulatory T cells

Blood ◽  
2016 ◽  
Vol 127 (1) ◽  
pp. 91-101 ◽  
Author(s):  
Eveline M. Delemarre ◽  
Theo van den Broek ◽  
Gerdien Mijnheer ◽  
Jenny Meerding ◽  
Ellen J. Wehrens ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Regulatory T Cells ◽  
Stem Cell Transplantation ◽  
Clinical Improvement ◽  
Autologous Stem Cell Transplantation ◽  
T Cell Reconstitution ◽  
Key Points ◽  
Autologous Hsct

Key Points Autologous HSCT induces functional renewal of regulatory T cells as well as a strong Treg TCR diversification in autoimmune patients. Adding regulatory T cells to the graft does not lead to additional clinical improvement but results in delayed donor T-cell reconstitution.

scholarly journals CD38 Correlates with an Immunosuppressive Treg Phenotype in Lupus-Prone Mice

2021 ◽  
Vol 22 (21) ◽  
pp. 11977
Author(s):  
Jocelyn C. Pérez-Lara ◽  
Enrique Espinosa ◽  
Leopoldo Santos-Argumedo ◽  
Héctor Romero-Ramírez ◽  
Gabriela López-Herrera ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Immune Activation ◽  
Lupus Erythematosus ◽  
Clinical Signs ◽  
Foxp3 Expression ◽  
Cell Receptor ◽  
Treg Cells ◽  
Transmembrane Glycoprotein ◽  
Ifn Γ

CD38 is a transmembrane glycoprotein expressed by T-cells. It has been reported that patients with systemic lupus erythematosus (SLE) showed increased CD38+CD25+ T-cells correlating with immune activation and clinical signs. Contrariwise, CD38 deficiency in murine models has shown enhanced autoimmunity development. Recent studies have suggested that CD38+ regulatory T-cells are more suppressive than CD38− regulatory T-cells. Thus, we have suggested that CD38 overexpression in SLE patients could play a role in regulating immune activation cells instead of enhancing it. This study found a correlation between CD38 with FoxP3 expression and immunosuppressive molecules (CD69, IL-10, CTLA-4, and PD-1) in T-cells from lupus-prone mice (B6.MRL-Faslpr/J). Additionally, B6.MRL-Faslpr/J mice showed a decreased proportion of CD38+ Treg cells regarding wild-type mice (WT). Furthermore, Regulatory T-Cells (Treg cells) from CD38-/- mice showed impairment in expressing immunosuppressive molecules and proliferation after stimulation through the T-cell receptor (TCR). Finally, we demonstrated an increased ratio of IFN-γ/IL-10 secretion in CD38-/- splenocytes stimulated with anti-CD3 compared with the WT. Altogether, our data suggest that CD38 represents an element in maintaining activated and proliferative Treg cells. Consequently, CD38 could have a crucial role in immune tolerance, preventing SLE development through Treg cells.

scholarly journals Targeting neuropilin-1 suppresses the stability of CD4+CD25+ regulatory T cells via the NF-κB signaling pathway in sepsis

2020 ◽  
Author(s):  
Yu-lei Gao ◽  
Chun-xue Wang ◽  
Zi-yi Wang ◽  
Wen-jie Li ◽  
Yan-cun Liu ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Signaling Pathway ◽  
Binding Activity ◽  
Dna Binding Activity ◽  
Sepsis Model ◽  
The Stability ◽  
The Impact ◽  
Tgf Β1

Neuropilin (Nrp)-1 contributes to maintain the stability of CD4+CD25+ regulatory T cells (Tregs). We investigated the impact of Nrp-1 on the stability of CD4+CD25+ Tregs, and the underlying signaling pathways, in a sepsis model. Splenic CD4+CD25+ Tregs were treated with anti-Nrp-1, or transfected to silence Nrp-1 and ikkβ, or administered with PDTC, followed by rSema3A in sepsis simulation. After creation of a sepsis model in mice, anti-Nrp-1 was administered. Expression of foxp3- TSDR, apoptosis rate, Foxp-3/CTLA-4/TGF-β1, IL-10 and TGF-β1, and NF-κB signaling activity of CD4+CD25+ Tregs were determined. Sepsis simulation with or without rSema3A increased the stability of CD4+CD25+ Tregs, including an increase in the expression of Foxp-3/CTLA-4/TGF-β1, decrease in apoptosis and methylation of foxp3- TSDR, increase in the secretion of TGF-β1 and IL-10, and increase in the immunosuppressive effect on CD4+T lymphocytes. silencing of Nrp-1 or anti-Nrp-1 treatment interdicted LPS stimulation with or without a rSema3A-mediated effect. Sepsis simulation increased the DNA-binding activity of NF-κB, as well as the p-ikkβ/ikkβ and p-P65/P65 ratios in vitro and vivo. Silencing of ikkβ expression or PDTC treatment suppressed the stability of CD4+CD25+ Tregs in LPS-induced sepsis. Weakening Nrp-1 reduced the stability of CD4+CD25+ Tregs by regulating the NF-κB signaling pathway, and could be a new target for immunoregulation in sepsis.

scholarly journals FOXP3 in Melanoma with Regression: Between Tumoral Expression and Regulatory T Cell Upregulation

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Mirela Cioplea ◽  
Luciana Nichita ◽  
Daniela Georgescu ◽  
Liana Sticlaru ◽  
Alexandra Cioroianu ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Regulatory T Cells ◽  
Tumor Cells ◽  
Retrospective Cohort ◽  
Poor Prognosis ◽  
Tumor Regression ◽  
Foxp3 Expression ◽  
Immune Defense ◽  
Stromal Microenvironment

Cutaneous melanoma is a significant immunogenic tumoral model, the most frequently described immune phenomenon being tumor regression, as a result of the interaction of tumoral antigens and stromal microenvironment. We present a retrospective cohort study including 52 cases of melanoma with regression. There were evaluated correlations of the most important prognostic factors (Breslow depth and mitotic index) with FOXP3 expression in tumor cells and with the presence of regulatory T cells and dendritic cells in the tumoral stroma. FOXP3 expression in tumor cells seems an independent factor of poor prognosis in melanoma, while regression areas are characterized by a high number of dendritic cells and a low number of regulatory T cells. FOXP3 is probably a useful therapeutical target in melanoma, since inhibition of FOXP3-positive tumor clones and of regulatory T cells could eliminate the ability of tumor cells to escape the immune defense of the host.

The NF-κB signalling pathway is involved in the LPS/IL-2-induced upregulation of FoxP3 expression in human CD4+CD25high regulatory T cells

2010 ◽  
Vol 19 (1) ◽  
pp. 29-37 ◽  
Author(s):  
Linda Milkova ◽  
Verena Voelcker ◽  
Inka Forstreuter ◽  
Ulrich Sack ◽  
Ulf Anderegg ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Foxp3 Expression ◽  
Signalling Pathway

scholarly journals Regulatory T Cells, a Potent Immunoregulatory Target for CAM Researchers: The Ultimate Antagonist (I)

2006 ◽  
Vol 3 (1) ◽  
pp. 25-30 ◽  
Author(s):  
Aristo Vojdani ◽  
Jonathan Erde
Keyword(s):  
T Cells ◽  
Immune System ◽  
Regulatory T Cells ◽  
Host Defense ◽  
Western Medicine ◽  
Treg Cells ◽  
Active Suppression ◽  
Beneficial Effects ◽  
The Past ◽  
Powerful Means

Over the past decade, great interest has been given to regulatory T (Treg) cells. A vast body of evidence has shown the existence and highlighted the importance of Treg cells in the active suppression of immune system responses. This form of immunoregulation is the dominant means utilized by the immune system to reach a harmony between reciprocal response processes in order to ensure adequate host defense with minimal host detriment. Therapeutically targeting Treg cells is a direct and powerful means to manipulate the immune system to achieve beneficial effects on various disease pathologies, including allergy, autoimmunity and cancer, as well as the facilitation of organ transplantation. This powerful target for immunoregulation is of much concern to practitioners and researchers of complementary and alternative medicine because it allows a great deal of control and certainty in dealing with the prevalence of debilitating immune system-related disorders for which there has been little remedy outside of Western Medicine.

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