scholarly journals Regulation of Suppressors of Cytokine Signaling as a Therapeutic Approach in Autoimmune Diseases, with an Emphasis on Multiple Sclerosis

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Vinod S. Ramgolam ◽  
Silva Markovic-Plese
Keyword(s):  
Multiple Sclerosis ◽  
Cell Differentiation ◽  
Autoimmune Diseases ◽  
Th17 Cell ◽  
Inflammatory Cells ◽  
Cytokine Signaling ◽  
Rapid Induction ◽  
Th17 Cell Differentiation ◽  
Socs3 Expression ◽  
Attractive Therapeutic Target

Multiple sclerosis (MS) is an inflammatory demyelinating, presumably autoimmune disease of the central nervous system (CNS). Among the available MS therapies, interferon (IFN)β and the recently introduced statins have been reported to exert their immunomodulatory effects through the induction of SOCS1 and SOCS3 in various inflammatory cell subsets. The SOCS proteins negatively regulate cytokine and Toll-like receptors- (TLR-) induced signaling in the inflammatory cells. SOCS1 and SOCS3 have been reported to play an important role in the regulation of Th17-cell differentiation through their effects on the cells of the innate and adaptive immune systems. IFNβ and statins inhibit Th17-cell differentiation directly and indirectly via induction of SOCS1 and SOCS3 expression in monocytes, dendritic cells (DCs), and B-cells. Due to their rapid induction and degradation, and SOCS-mediated regulation of multiple cytokine-signaling pathways, they represent an attractive therapeutic target in the autoimmune diseases, and particularly relapsing remitting (RR) MS.

The role of metabolism in Th17 cell differentiation and autoimmune diseases

2022 ◽  
Vol 103 ◽  
pp. 108450
Author(s):  
Guang Wang ◽  
Zehong Su ◽  
Hui Li ◽  
Li Xiao ◽  
Chengyue Li ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Autoimmune Diseases ◽  
Th17 Cell ◽  
Th17 Cell Differentiation

scholarly journals ZEB1 promotes pathogenic Th1 and Th17 cell differentiation in multiple sclerosis

Cell Reports ◽  
2021 ◽  
Vol 36 (8) ◽  
pp. 109602
Author(s):  
Yuan Qian ◽  
Gabriel Arellano ◽  
Igal Ifergan ◽  
Jean Lin ◽  
Caroline Snowden ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cell Differentiation ◽  
Th17 Cell ◽  
Th17 Cell Differentiation

scholarly journals PD-L1 up-regulation restrains Th17 cell differentiation in STAT3 loss- and STAT1 gain-of-function patients

2017 ◽  
Vol 214 (9) ◽  
pp. 2523-2533 ◽  
Author(s):  
Yuan Zhang ◽  
Chi A. Ma ◽  
Monica G. Lawrence ◽  
Timothy J. Break ◽  
Michael P. O’Connell ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Genetic Diseases ◽  
Cytokine Signaling ◽  
Loss Of Function ◽  
Th17 Cell Differentiation ◽  
Socs3 Expression ◽  
Th17 Differentiation ◽  
Cytokine Stimulation ◽  
Cellular Phenotypes

Patients with hypomorphic mutations in STAT3 and patients with hypermorphic mutations in STAT1 share several clinical and cellular phenotypes suggesting overlapping pathophysiologic mechanisms. We, therefore, examined cytokine signaling and CD4+ T cell differentiation in these cohorts to characterize common pathways. As expected, differentiation of Th17 cells was impaired in both cohorts. We found that STAT1 was hyperphosphorylated in response to cytokine stimulation in both cohorts and that STAT1-dependent PD-L1 up-regulation—known to inhibit Th17 differentiation in mouse models—was markedly enhanced as well. Overexpression of SOCS3 strongly inhibited phosphorylation of STAT1 and PD-L1 up-regulation, suggesting that diminished SOCS3 expression may lead to the observed effects. Defects in Th17 differentiation could be partially overcome in vitro via PD-L1 inhibition and in a mouse model of STAT3 loss-of-function by crossing them with PD-1 knockout mice. PD-L1 may be a potential therapeutic target in several genetic diseases of immune deficiency affecting cytokine signaling.

scholarly journals Cannabinoids drive Th17 cell differentiation in patients with rheumatic autoimmune diseases

2020 ◽  
Author(s):  
Konstantin Kotschenreuther ◽  
Iris Waqué ◽  
Shuaifeng Yan ◽  
Anja Meyer ◽  
Thom Haak ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Autoimmune Diseases ◽  
Th17 Cell ◽  
Th17 Cell Differentiation

scholarly journals miRNAs Alter T Helper 17 Cell Fate in the Pathogenesis of Autoimmune Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Junxia Huang ◽  
Xinzhi Xu ◽  
Ji Yang
Keyword(s):  
Immune Response ◽  
Cell Differentiation ◽  
Autoimmune Diseases ◽  
Cell Fate ◽  
Th17 Cell ◽  
Th17 Cells ◽  
T Helper ◽  
T Helper 17 ◽  
Th17 Cell Differentiation ◽  
And Function

T helper 17 (Th17) cells are characterized by the secretion of the IL-17 cytokine and are essential for the immune response against bacterial and fungal infections. Despite the beneficial roles of Th17 cells, unrestrained IL-17 production can contribute to immunopathology and inflammatory autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. Although these diverse outcomes are directed by the activation of Th17 cells, the regulation of Th17 cells is incompletely understood. The discovery that microRNAs (miRNAs) are involved in the regulation of Th17 cell differentiation and function has greatly improved our understanding of Th17 cells in immune response and disease. Here, we provide an overview of the biogenesis and function of miRNA and summarize the role of miRNAs in Th17 cell differentiation and function. Finally, we focus on recent advances in miRNA-mediated dysregulation of Th17 cell fate in autoimmune diseases.

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