Lymphocytes T Helper 17 in Multiple Sclerosis: Regulation by Intestinal Microbiota

Uncontrolled activity of T cells mediates autoimmune and inflammatory diseases such as multiple sclerosis, inflammatory bowel diseases, rheumatoid arthritis, type 1 diabetes, and atherosclerosis. Recent findings suggest that enhanced activity of interleukin-17 (IL-17) producing T helper 17 cells (Th17 cells) plays an important role in autoimmune diseases and inflammatory diseases. Previous papers have revealed that a lipid-lowering synthetic ligand of peroxisome proliferator-activated receptorα(PPARα), fenofibrate, alleviates both atherosclerosis and a few nonlipid-associated autoimmune diseases such as autoimmune colitis and multiple sclerosis. However, the link between fenofibrate and Th17 cells is lacking. In the present study, we hypothesized that fenofibrate inhibited the differentiation of Th17 cells. Our results showed that fenofibrate inhibited transforming growth factor-β(TGF-β) and IL-6-induced differentiation of Th17 cellsin vitro. However, other PPARαligands such as WY14643, GW7647 and bezafibrate did not show any effect on Th17 differentiation, indicating that this effect of fenofibrate might be PPARαindependent. Furthermore, our data showed that fenofibrate reduced IL-21 production and STAT3 activation, a critical signal in the Th17 differentiation. Thus, by ameliorating the differentiation of Th17 cells, fenofibrate might be beneficial for autoimmunity and inflammatory diseases.

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Distinct Expression of Inflammatory Features in T Helper 17 Cells from Multiple Sclerosis Patients

Cells ◽

10.3390/cells8060533 ◽

2019 ◽

Vol 8 (6) ◽

pp. 533 ◽

Cited By ~ 6

Author(s):

Alessia Capone ◽

Manuela Bianco ◽

Gabriella Ruocco ◽

Marco De Bardi ◽

Luca Battistini ◽

...

Keyword(s):

Multiple Sclerosis ◽

T Cells ◽

Cd4 T Cells ◽

Th17 Cells ◽

Chronic Inflammatory Disease ◽

T Helper ◽

T Helper 17 ◽

Inflammatory Status ◽

Healthy Donors ◽

Multiple Sclerosis Patients

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). T helper (Th) 17 lymphocytes play a role in the pathogenesis of MS. Indeed, Th17 cells are abundant in the cerebrospinal fluid and peripheral blood of MS patients and promote pathogenesis in the mouse model of MS. To gain insight into the function of Th17 cells in MS, we tested whether Th17 cells polarized from naïve CD4 T cells of healthy donors and MS patients display different features. To this end, we analysed several parameters that typify the Th17 profile during the differentiation process of naïve CD4 T cells obtained from relapsing-remitting (RR)-MS patients (n = 31) and healthy donors (HD) (n = 28). Analysis of an array of cytokines produced by Th17 cells revealed that expression of interleukin (IL)-21, tumour necrosis factor (TNF)-β, IL-2 and IL-1R1 is significantly increased in Th17 cells derived from MS patients compared to healthy donor-derived cells. Interestingly, IL-1R1 expression is also increased in Th17 cells circulating in the blood of MS patients compared to healthy donors. Since IL-2, IL-21, TNF-β, and IL-1R1 play a crucial role in the activation of immune cells, our data indicate that high expression of these molecules in Th17 cells from MS patients could be related to their high inflammatory status.

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Psoriasis and Multiple Sclerosis: Is There a Link?

Journal of Cutaneous Medicine and Surgery ◽

10.2310/7750.2010.09063 ◽

2010 ◽

Vol 14 (4) ◽

pp. 151-155 ◽

Cited By ~ 11

Author(s):

Tiffany Kwok ◽

Wei Jing Loo ◽

Lyn Guenther

Keyword(s):

Multiple Sclerosis ◽

Case Series ◽

Cochrane Library ◽

Review Of The Literature ◽

T Helper ◽

Canadian Study ◽

T Helper 17 ◽

Increased Risk ◽

Genetic Linkages ◽

Interleukin 23

Background: Psoriasis and multiple sclerosis (MS) are both autoimmune T cell-mediated diseases. Some case series have suggested an association. Objective: To investigate the potential relationship between psoriasis and MS based on a systematic review of the literature. Methods: Medline, Cochrane Library, and EMBASE searches were performed. Results: T-helper 17 cells are involved in the pathogenesis of both psoriasis and MS. Both conditions have been associated with interleukin-23 receptor (IL23R) polymorphisms. Studies have reported psoriasis in 0.41 to 7.7% of individuals with MS. A higher rate of psoriasis compared to controls was noted in a few small MS cohorts, but the number of cases was too small to draw any firm conclusions. In two studies, including a large Canadian study of 5,031 patients with MS, there was no increased prevalence of psoriasis in patients over the control population. Family members of individuals with MS do not appear to be at increased risk for psoriasis in these studies. Psoriasis has developed during treatment for MS, and MS has developed during treatment for psoriasis. Conclusion: Although there are some common genetic linkages in psoriasis and MS, psoriasis does not appear to be more common in patients with MS or their relatives.

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Th17 cells: A prognostic marker for MS rebound after natalizumab cessation?

Multiple Sclerosis Journal ◽

10.1177/1352458516640609 ◽

2016 ◽

Vol 23 (1) ◽

pp. 114-118 ◽

Cited By ~ 13

Author(s):

Jürgen Haas ◽

Katharina Schneider ◽

Alexander Schwarz ◽

Mirjam Korporal-Kuhnke ◽

Simon Faller ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disease Activity ◽

Prognostic Marker ◽

Peripheral Blood ◽

Th17 Cell ◽

Th17 Cells ◽

T Helper ◽

T Helper 17 ◽

Blood Samples ◽

Cytokine Levels

Background: Multiple sclerosis (MS) patients are at risk of renewed disease activity after discontinuing natalizumab (NAT) treatment. Objective: Assessing the implication of T helper 17 (Th17) cells in MS reactivation after NAT cessation. Methods: We monitored frequencies of Th17 cells and interleukin (IL)-17 cytokine levels in blood samples of 57 MS patients, without, during, and after NAT exposure. Results: Frequencies of both Th17 cells and, in part, also IL-17 levels, in peripheral blood increased under prolonged NAT therapy, returned to baseline after NAT withdrawal and became almost undetectable in blood samples of individuals who experienced relapses during the wash-out phase. Conclusion: Assessing the Th17-cell/IL-17 axis might help to predict rebound MS activity after NAT withdrawal.

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Dysregulated MicroRNA Involvement in Multiple Sclerosis by Induction of T Helper 17 Cell Differentiation

Frontiers in Immunology ◽

10.3389/fimmu.2018.01256 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 20

Author(s):

Chen Chen ◽

Yifan Zhou ◽

Jingqi Wang ◽

Yaping Yan ◽

Lisheng Peng ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cell Differentiation ◽

T Helper ◽

T Helper 17 ◽

T Helper 17 Cell

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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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