The role of TH17 cells in multiple sclerosis: Therapeutic implications

: The role of gut microbiota in health and diseases has been receiving increased attention recently. Emerging evidence from previous studies on the gut-microbiota-brain axis highlighted the importance of gut microbiota in neurological disorders. Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system (CNS) resulting from T-cell-driven, myelin-directed autoimmunity. The dysbiosis of gut microbiota in MS patients has been reported in published research studies, indicating that gut microbiota plays an important role in the pathogenesis of MS. Gut microbiota has also been reported to influence the initiation of disease and severity of experimental autoimmune encephalomyelitis, which is the animal model of MS. However, the underlying mechanisms of gut microbiota involvement in the pathogenesis of MS remain unclear. Therefore, in this review, we summerized the potential mechanisms for gut microbiota involvement in the pathogenesis of MS, including increasing the permeability of the intestinal barrier, initiating an autoimmune response, disrupting the blood-brain barrier integrity, and contributing to chronic inflammation. The possibility for gut microbiota as a target for MS therapy has also been discussed. This review provides new insight into understanding the role of gut microbiota in neurological and inflammatory diseases.

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The role of adhesion molecules in multiple sclerosis: biology, pathogenesis and therapeutic implications

Molecular Medicine Today ◽

10.1016/s1357-4310(97)01066-6 ◽

1997 ◽

Vol 3 (7) ◽

pp. 310-321 ◽

Cited By ~ 33

Author(s):

Juan J. Archelos ◽

Hans-Peter Hartung

Keyword(s):

Multiple Sclerosis ◽

Adhesion Molecules ◽

Therapeutic Implications

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Th17 Cells Pathways in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders: Pathophysiological and Therapeutic Implications

Mediators of Inflammation ◽

10.1155/2016/5314541 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 40

Author(s):

Giordani Rodrigues Dos Passos ◽

Douglas Kazutoshi Sato ◽

Jefferson Becker ◽

Kazuo Fujihara

Keyword(s):

Multiple Sclerosis ◽

Environmental Factors ◽

Neuromyelitis Optica ◽

Th17 Cells ◽

Inflammatory Cells ◽

New Drugs ◽

Neuromyelitis Optica Spectrum Disorders ◽

T Helper 17 ◽

Therapeutic Implications ◽

Spectrum Disorders

Several animal and human studies have implicated CD4+ T helper 17 (Th17) cells and their downstream pathways in the pathogenesis of central nervous system (CNS) autoimmunity in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), challenging the traditional Th1-Th2 paradigm. Th17 cells can efficiently cross the blood-brain barrier using alternate ways from Th1 cells, promote its disruption, and induce the activation of other inflammatory cells in the CNS. A number of environmental factors modulate the activity of Th17 pathways, so changes in the diet, exposure to infections, and other environmental factors can potentially change the risk of development of autoimmunity. Currently, new drugs targeting specific points of the Th17 pathways are already being tested in clinical trials and provide basis for the development of biomarkers to monitor disease activity. Herein, we review the key findings supporting the relevance of the Th17 pathways in the pathogenesis of MS and NMOSD, as well as their potential role as therapeutic targets in the treatment of immune-mediated CNS disorders.

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Prediction of probable impact of miR-34a and miR-215 on differentiation of naive CD4+ T cells to Th17 cells in multiple sclerosis

Journal of Shahrekord University of Medical Sciences ◽

10.34172/jsums.2019.48 ◽

2018 ◽

Vol 21 (6) ◽

pp. 276-279

Author(s):

Nooshin Ghadiri ◽

Aref Hoseini ◽

Kamran Ghaedi ◽

Negar Alsadat Emamnia ◽

Mazdak Ganjalikhani-Hakemi ◽

...

Keyword(s):

Multiple Sclerosis ◽

Th17 Cells ◽

Therapeutic Approaches ◽

Diagnostic Biomarkers ◽

Cellular Processes ◽

High Prevalence ◽

Probable Impact ◽

Non Coding Rnas ◽

Th17 Differentiation

Background and aims: miRNAs, as a class of non-coding RNAs, take part in different cellular processes. Dysregulation of different miRNAs has been reported in numerous disorders to date. Multiple sclerosis (MS) is an autoimmune disease with high prevalence in Iran and Th17 cells play an important role in its pathogenesis. In the current study, we aimed to predict the possible role of miR-34a and miR-215 in the process of controlling Th17 differentiation, and hence, their possible impact on the onset and progression of MS. Methods: We investigated probable interactions of miRNAs and genes that participate in Th17 cells differentiation using miRwalk database as an integrative one which utilizes 10 different algorithms to predict miRNA-mRNA interaction. Results: Based on our findings, miR-34a and miR-215 were predicted to have a potential role in the induction of Th17 cells differentiation. Conclusion: Conclusively, miR-34a and miR-215 may up-regulate Th17 cells of MS patients. Since bioinformatics data have shown that these miRNAs suppress negative regulatory genes in Th17 cells differentiation, we suppose that down-regulation of these miRNAs could ameliorate MS symptoms. Therefore, several therapeutic approaches may be considered for these miRNAs besides their application as valuable prognostic/diagnostic biomarkers in detection of various stages of MS.

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Advances in T Helper 17 Cell Biology: Pathogenic Role and Potential Therapy in Multiple Sclerosis

Mediators of Inflammation ◽

10.1155/2015/475158 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 27

Author(s):

Elisabetta Volpe ◽

Luca Battistini ◽

Giovanna Borsellino

Keyword(s):

Multiple Sclerosis ◽

Cell Biology ◽

Th17 Cells ◽

Bacterial Infections ◽

Demyelinating Diseases ◽

T Helper ◽

Pathogenic Role ◽

T Helper 17 ◽

Effector Cytokines

The discovery of the T helper (Th) 17 lineage, involved in the protection against fungal and extracellular bacterial infections, has profoundly revolutionized our current understanding of T cell-mediated responses in autoimmune diseases, including multiple sclerosis (MS). Indeed, recent data demonstrate the pathogenic role of Th17 cells in autoimmune disorders. In particular, studies in MS and in its animal model (EAE, experimental autoimmune encephalomyelitis) have revealed a crucial role of Th17 cells in the pathogenesis of autoimmune demyelinating diseases in both mice and humans. Over the past years, several important aspects concerning Th17 cells have been elucidated, such as the factors which promote or inhibit their differentiation and the effector cytokines which mediate their responses. The identification of the features endowing Th17 cells with high pathogenicity in MS is of particular interest, and discoveries in Th17 cell biology and function could lead to the design of new strategies aimed at modulating the immune response in MS. Here, we will discuss recent advances in this field, with particular focus on the mechanisms conferring pathogenicity in MS and their potential modulation.

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Altered Immunoregulation in Rheumatoid Arthritis: The Role of Regulatory T Cells and Proinflammatory Th17 Cells and Therapeutic Implications

Mediators of Inflammation ◽

10.1155/2015/751793 ◽

2015 ◽

Vol 2015 ◽

pp. 1-12 ◽

Cited By ~ 46

Author(s):

Alessia Alunno ◽

Mirko Manetti ◽

Sara Caterbi ◽

Lidia Ibba-Manneschi ◽

Onelia Bistoni ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Th17 Cells ◽

Current Knowledge ◽

Cell Subset ◽

Treg Cells ◽

Lymphocyte Subpopulations ◽

Therapeutic Targeting ◽

Therapeutic Implications ◽

T Lymphocyte Subpopulations

In recent years several studies investigated the role of T lymphocyte subpopulations in the pathogenesis of rheumatoid arthritis (RA). Pathogenic Th17 cells mediate pannus growth, osteoclastogenesis, and synovial neoangiogenesis; hence they are key players in the development of the disease. On the other hand, regulatory T (Treg) cells are a T cell subset whose peculiar function is to suppress autoreactive lymphocytes. The imbalance between Th17 and Treg cells has been identified as a crucial event in the pathogenesis of RA. In addition, the effects of currently employed RA therapeutic strategies on these lymphocyte subpopulations have been extensively investigated. This review article aims to discuss current knowledge on Treg and Th17 cells in RA and possible implications of their therapeutic targeting in this disorder.

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