Cannabinoids drive Th17 cell differentiation in patients with rheumatic autoimmune diseases

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.

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

Frontiers in Immunology ◽

10.3389/fimmu.2021.593473 ◽

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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Suppression of Th17 cell differentiation by misshapen/NIK-related kinase MINK1

Journal of Experimental Medicine ◽

10.1084/jem.20161120 ◽

2017 ◽

Vol 214 (5) ◽

pp. 1453-1469 ◽

Cited By ~ 19

Author(s):

Guotong Fu ◽

Qin Xu ◽

Yuanjun Qiu ◽

Xuexiao Jin ◽

Ting Xu ◽

...

Keyword(s):

Cell Differentiation ◽

Autoimmune Diseases ◽

Th17 Cell ◽

Th17 Cells ◽

Suppressive Effect ◽

Dependent Manner ◽

Autoimmune Encephalomyelitis ◽

Th17 Cell Differentiation ◽

Ros Scavenger ◽

Experimental Autoimmune

T helper type 17 cells (Th17 cells) are major contributors to many autoimmune diseases. In this study, we demonstrate that the germinal center kinase family member MINK1 (misshapen/NIK-related kinase 1) negatively regulates Th17 cell differentiation. The suppressive effect of MINK1 on induction of Th17 cells is mediated by the inhibition of SMAD2 activation through direct phosphorylation of SMAD2 at the T324 residue. The importance of MINK1 to Th17 cell differentiation was strengthened in the animal model of experimental autoimmune encephalomyelitis (EAE). Moreover, we show that the reactive oxygen species (ROS) scavenger N-acetyl cysteine boosts Th17 cell differentiation in a MINK1-dependent manner and exacerbates the severity of EAE. Thus, we have not only established MINK1 as a critical regulator of Th17 cell differentiation, but also clarified that accumulation of ROS may limit the generation of Th17 cells. The contribution of MINK1 to ROS-regulated Th17 cell differentiation may suggest an important mechanism for the development of autoimmune diseases influenced by antioxidant dietary supplements.

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