scholarly journals Human CD39hi regulatory T cells present stronger stability and function under inflammatory conditions

2016 ◽  
Vol 14 (6) ◽  
pp. 521-528 ◽  
Author(s):  
Jian Gu ◽  
Xuhao Ni ◽  
Xiongxiong Pan ◽  
Hao Lu ◽  
Yunjie Lu ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Inflammatory Conditions ◽  
And Function

scholarly journals Regulatory T cell expansion by a highly CD25-dependent IL-2 mutein arrests ongoing autoimmunity

2019 ◽  
Author(s):  
Liliane Khoryati ◽  
Minh Nguyet Pham ◽  
McKenna Sherve ◽  
Swarnima Kumari ◽  
Kevin Cook ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Dose Range ◽  
Interleukin 2 ◽  
Autoimmune Response ◽  
Wild Type ◽  
Effector Cells ◽  
Inflammatory Conditions ◽  
Receptor Component ◽  
And Function

AbstractInterleukin-2 (IL-2) controls the homeostasis and function of regulatory T cells (Tregs) and defects in the IL-2 pathway contribute to multiple autoimmune diseases. Although recombinant IL-2 therapy has been efficacious in certain inflammatory conditions, the capacity for IL-2 to also activate inflammatory effector responses highlights the need for IL-2-based therapeutics with improved Treg-specificity. From a panel of rationally designed IL-2 variants, we identified IL-2 muteins with reduced potency and enhanced Treg-selectivity due to increased dependence on the IL-2-receptor component CD25. As an Fc-fused homodimer, the optimal Fc.IL-2 mutein induced selective Treg enrichment and reduced agonism of effector cells across a wide dose range. Furthermore, despite being a weaker agonist, overall Treg growth was greater and more sustained due to reduced receptor-mediated clearance of the Fc.IL-2 mutein compared to Fc-fused wild-type IL-2. Preferential Treg enrichment was also observed in the presence of activated pathogenic T cells in the autoimmune target organ, despite a loss of Treg-selectivity in an IL-2R-proximal response. These features allowed for extended resolution of spontaneous autoimmunity using infrequent dosing schedules. Thus, IL-2 muteins enable efficient, flexible, and targeted control of the autoimmune response.One Sentence SummaryA CD25-dependent IL-2 mutein selectively expands regulatory T cells and provides potent and targeted control of autoimmunity.

scholarly journals SOCS1 and Regulation of Regulatory T Cells Plasticity

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Reiko Takahashi ◽  
Akihiko Yoshimura
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Molecular Mechanisms ◽  
Foxp3 Expression ◽  
Negative Regulator ◽  
Cytokine Signaling ◽  
Cell Integrity ◽  
Inflammatory Conditions ◽  
A Minor ◽  
And Function

Several reports have suggested that natural regulatory T cells (Tregs) lose Forkhead box P3 (Foxp3) expression and suppression activity under certain inflammatory conditions. Treg plasticity has been studied because it may be associated with the pathogenesis of autoimmunity. Some studies showed that a minor uncommitted Foxp3+T cell population, which lacks hypomethylation at Treg-specific demethylation regions (TSDRs), may convert to effector/helper T cells. Suppressor of cytokine signaling 1 (SOCS1), a negative regulator of cytokine signaling, has been reported to play an important role in Treg cell integrity and function by protecting the cells from excessive inflammatory cytokines. In this review, we discuss Treg plasticity and maintenance of suppression functions in both physiological and pathological settings. In addition, we discuss molecular mechanisms of maintaining Treg plasticity by SOCS1 and other molecules. Such information will be useful for therapy of autoimmune diseases and reinforcement of antitumor immunity.

scholarly journals Balancing Inflammation: The Link between Th17 and Regulatory T Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Maggie L. Diller ◽  
Ragini R. Kudchadkar ◽  
Keith A. Delman ◽  
David H. Lawson ◽  
Mandy L. Ford
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Th17 Cells ◽  
Cell Lineage ◽  
Effector Functions ◽  
Inflammatory Conditions ◽  
Cell Compartments ◽  
Th17 Cell Differentiation ◽  
And Function

CD4+T cell compartments in mouse and man are composed of multiple distinct subsets each possessing unique phenotypic and functional characteristics. IL-17-producing CD4+T cells (Th17 cells) represent a distinct subset of the CD4+T cell lineage. Recent evidence suggests that Th17 cells carry out effector functions similar to cytotoxic CD8+T cells and play an important role in the clearance of extracellular pathogens and fungi. Th17 cell differentiation and function are closely related to the development and function of regulatory T cells(TREG). The balance between these two cell populations is essential for immune homeostasis and dysregulation of this balance has been implicated in a variety of inflammatory conditions including autoimmunity, allograft rejection, and tumorigenesis. Emerging evidence reports a significant amount of plasticity between the Th17 and regulatory T cell compartments, and the mechanisms by which these cells communicate and influence each other are just beginning to be understood. In this review, we highlight recent findings detailing the mechanisms driving Th17 andTREGplasticity and discuss the biologic consequences of their unique relationship.

scholarly journals Progranulin Facilitates Conversion and Function of Regulatory T Cells under Inflammatory Conditions

PLoS ONE ◽  
2014 ◽  
Vol 9 (11) ◽  
pp. e112110 ◽  
Author(s):  
Fanhua Wei ◽  
Yuying Zhang ◽  
Weiming Zhao ◽  
Xiuping Yu ◽  
Chuan-ju Liu
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Inflammatory Conditions ◽  
And Function

scholarly journals Trichostatin A Promotes the Generation and Suppressive Functions of Regulatory T Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Cristian Doñas ◽  
Macarena Fritz ◽  
Valeria Manríquez ◽  
Gabriela Tejón ◽  
María Rosa Bono ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Trichostatin A ◽  
Gene Promoter ◽  
Treg Cells ◽  
Specific Subset ◽  
Global Increase ◽  
And Function ◽  
H3 Acetylation

Regulatory T cells are a specific subset of lymphocytes that suppress immune responses and play a crucial role in the maintenance of self-tolerance. They can be generated in the thymus as well as in the periphery through differentiation of naïve CD4+T cells. The forkhead box P3 transcription factor (Foxp3) is a crucial molecule regulating the generation and function of Tregs. Here we show that thefoxp3gene promoter becomes hyperacetylated inin vitrodifferentiated Tregs compared to naïve CD4+T cells. We also show that the histone deacetylase inhibitor TSA stimulated thein vitrodifferentiation of naïve CD4+T cells into Tregs and that this induction was accompanied by a global increase in histone H3 acetylation. Importantly, we also demonstrated that Tregs generated in the presence of TSA have phenotypical and functional differences from the Tregs generated in the absence of TSA. Thus, TSA-generated Tregs showed increased suppressive activities, which could potentially be explained by a mechanism involving the ectonucleotidases CD39 and CD73. Our data show that TSA could potentially be used to enhance the differentiation and suppressive function of CD4+Foxp3+Treg cells.

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