scholarly journals Fenofibrate Inhibited the Differentiation of T Helper 17 CellsIn Vitro

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Zhou Zhou ◽  
Weiliang Sun ◽  
Ying Liang ◽  
Yanxiang Gao ◽  
Wei Kong ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Autoimmune Diseases ◽  
Th17 Cells ◽  
Transforming Growth Factor ◽  
Inflammatory Diseases ◽  
Lipid Lowering ◽  
Interleukin 17 ◽  
T Helper ◽  
T Helper 17 ◽  
Th17 Differentiation

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.

scholarly journals Pivotal Roles of T-Helper 17-Related Cytokines, IL-17, IL-22, and IL-23, in Inflammatory Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Ning Qu ◽  
Mingli Xu ◽  
Izuru Mizoguchi ◽  
Jun-ichi Furusawa ◽  
Kotaro Kaneko ◽  
...  
Keyword(s):  
Th17 Cell ◽  
Th17 Cells ◽  
Functional Role ◽  
Inflammatory Diseases ◽  
Interleukin 17 ◽  
T Helper ◽  
T Helper 17 ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

T-helper 17 (Th17) cells are characterized by producing interleukin-17 (IL-17, also called IL-17A), IL-17F, IL-21, and IL-22 and potentially TNF-α and IL-6 upon certain stimulation. IL-23, which promotes Th17 cell development, as well as IL-17 and IL-22 produced by the Th17 cells plays essential roles in various inflammatory diseases, such as experimental autoimmune encephalomyelitis, rheumatoid arthritis, colitis, and Concanavalin A-induced hepatitis. In this review, we summarize the characteristics of the functional role of Th17 cells, with particular focus on the Th17 cell-related cytokines such as IL-17, IL-22, and IL-23, in mouse models and human inflammatory diseases.

scholarly journals T Helper 17 Cells in Autoimmune Liver Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Masanori Abe ◽  
Yoichi Hiasa ◽  
Morikazu Onji
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Autoimmune Diseases ◽  
Th17 Cells ◽  
Transforming Growth Factor ◽  
Treg Cells ◽  
Reciprocal Relationship ◽  
Th2 Cells ◽  
T Helper ◽  
T Helper 17

Many autoimmune diseases are driven by self-reactive T helper (Th) cells. A new population of effector CD4+T cells characterized by the secretion of interleukin (IL)-17, referred to as Th17 cells, has been demonstrated to be phenotypically, functionally, and developmentally distinct from Th1 and Th2 cells. Because the liver is known to be an important source of transforming growth factor-βand IL-6, which are cytokines that are crucial for Th17 differentiation, it is very likely that Th17 cells contribute to liver inflammation and autoimmunity. In contrast, another distinct subset of T cells, regulatory T cells (Treg), downregulate immune responses and play an important role in maintaining self-tolerance. In addition, there is a reciprocal relationship between Th17 cells and Tregs, in development and effector functions, and the balance between Th17 and Treg cells can affect the outcome of immune responses, particularly in autoimmune diseases. In this review, we will focus on the latest investigative findings related to Th17 cells in autoimmune liver disease.

scholarly journals Superantigenic Staphylococcus aureus Stimulates Production of Interleukin-17 from Memory but Not Naive T Cells

2009 ◽  
Vol 78 (1) ◽  
pp. 381-386 ◽  
Author(s):  
Ulrika Islander ◽  
Annica Andersson ◽  
Erika Lindberg ◽  
Ingegerd Adlerberth ◽  
Agnes E. Wold ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
T Cells ◽  
Th17 Cells ◽  
Mononuclear Cells ◽  
Memory T Cells ◽  
Inflammatory Diseases ◽  
Commensal Bacteria ◽  
Interleukin 17 ◽  
T Helper ◽  
T Helper 17

ABSTRACT T-helper 17 (Th17) cells are characterized by their production of interleukin-17 (IL-17) and have a role in the protection against infections and in certain inflammatory diseases. Humans who lack Th17 cells are more susceptible to Staphylococcus aureus infections compared to individuals having Th17 cells. S. aureus is part of the commensal skin microflora and also colonize the infant gut. To investigate whether UV-killed S. aureus would be more capable of inducing IL-17 than other commensal bacteria, we stimulated mononuclear cells from adults, infants, and newborns with various gram-positive and gram-negative commensal bacteria. IL-17 was produced from adult memory Th17 cells after stimulation with superantigen-producing S. aureus but not nonsuperantigenic S. aureus or other common commensal gut bacteria. Cells from newborns were poor IL-17 producers after stimulation with S. aureus, whereas in some cases IL-17 was secreted from cells isolated from infants at the age of 4 and 18 months. These results suggest that superantigenic S. aureus are particularly efficient in stimulating IL-17 production and that the cytokine is produced from memory T cells.

scholarly journals Trim33 mediates the proinflammatory function of Th17 cells

2018 ◽  
Vol 215 (7) ◽  
pp. 1853-1868 ◽  
Author(s):  
Shinya Tanaka ◽  
Yu Jiang ◽  
Gustavo J. Martinez ◽  
Kentaro Tanaka ◽  
Xiaowei Yan ◽  
...  
Keyword(s):  
Th17 Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Underlying Mechanism ◽  
T Helper ◽  
T Helper 17 ◽  
Th17 Differentiation ◽  
Expression Loss

Transforming growth factor–β (TGF-β) regulates reciprocal regulatory T cell (T reg) and T helper 17 (Th17) differentiation, the underlying mechanism of which is still not understood. Here, we report that tripartite motif-containing 33 (Trim33), a modulator of TGF-β signaling that associates with Smad2, regulates the proinflammatory function of Th17 cells. Trim33 deficiency in T cells ameliorated an autoimmune disease in vivo. Trim33 was required for induction in vitro of Th17, but not T reg cells. Moreover, Smad4 and Trim33 play contrasting roles in the regulation of IL-10 expression; loss of Trim33 enhanced IL-10 production. Furthermore, Trim33 was recruited to the Il17a and Il10 gene loci, dependent on Smad2, and mediated their chromatin remodeling during Th17 differentiation. Trim33 thus promotes the proinflammatory function of Th17 cells by inducing IL-17 and suppressing IL-10 expression.

scholarly journals Th17 Response and Inflammatory Autoimmune Diseases

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Janelle C. Waite ◽  
Dimitris Skokos
Keyword(s):  
Autoimmune Diseases ◽  
Th17 Cells ◽  
Potential Role ◽  
Interleukin 17 ◽  
Autoinflammatory Disorder ◽  
T Helper ◽  
Preclinical Models ◽  
T Helper 17 ◽  
Th17 Response ◽  
Proinflammatory Activity

The proinflammatory activity of T helper 17 (Th17) cells can be beneficial to the host during infection. However, uncontrolled or inappropriate Th17 activation has been linked to several autoimmune and autoinflammatory pathologies. Indeed, preclinical and clinical data show that Th17 cells are associated with several autoimmune diseases such as arthritis, multiple sclerosis, psoriasis, and lupus. Furthermore, targeting the interleukin-17 (IL-17) pathway has attenuated disease severity in preclinical models of autoimmune diseases. Interestingly, a recent report brings to light a potential role for Th17 cells in the autoinflammatory disorder adult-onset Still's disease (AOSD). Whether Th17 cells are the cause or are directly involved in AOSD remains to be shown. In this paper, we discuss the biology of Th17 cells, their role in autoimmune disease development, and in AOSD in particular, as well as the growing interest of the pharmaceutical industry in their use as therapeutic targets.

Faecalibacterium prausnitzii produces butyrate to decrease c-Myc-related metabolism and Th17 differentiation by inhibiting histone deacetylase 3

2019 ◽  
Vol 31 (8) ◽  
pp. 499-514 ◽  
Author(s):  
Mingming Zhang ◽  
Lixing Zhou ◽  
Yuming Wang ◽  
Robert Gregory Dorfman ◽  
Dehua Tang ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Th17 Cells ◽  
Inflammatory Diseases ◽  
T Helper 17 ◽  
Histone Deacetylase 3 ◽  
Faecalibacterium Prausnitzii ◽  
Other Substances ◽  
Th17 Differentiation ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Abstract Decreased levels of Faecalibacterium prausnitzii (F. prausnitzii), whose supernatant plays an anti-inflammatory effect, are frequently found in inflammatory bowel disease (IBD) patients. However, the anti-inflammatory products in F. prausnitzii supernatant and the mechanism have not been fully investigated. Here we found that F. prausnitzii and F. prausnitzii-derived butyrate were decreased in the intestines of IBD patients. Supplementation with F. prausnitzii supernatant and butyrate could ameliorate colitis in an animal model. Butyrate, but not other substances produced by F. prausnitzii, exerted an anti-inflammatory effect by inhibiting the differentiation of T helper 17 (Th17) cells. The mechanism underlying the anti-inflammatory effects of the butyrate produced by F. prausnitzii involved the enhancement of the acetylation-promoted degradation of c-Myc through histone deacetylase 3 (HDAC3) inhibition. In conclusion, F. prausnitzii produced butyrate to decrease Th17 differentiation and attenuate colitis through inhibiting HDAC3 and c-Myc-related metabolism in T cells. The use of F. prausnitzii may be an effective new approach to decrease the level of Th17 cells in the treatment of inflammatory diseases.

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

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 533 ◽  
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.

Abstract 075: Proinflammatory T Helper 17 Cells as an Indicator of Hypertension

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Seungbum Kim ◽  
Vermali Rodriguez ◽  
Carl J Pepine ◽  
Mohan K Raizada
Keyword(s):  
T Cells ◽  
Progenitor Cells ◽  
Th17 Cells ◽  
Human Study ◽  
Interleukin 17 ◽  
Ang Ii ◽  
T Helper ◽  
T Helper 17 ◽  
Important Indicator ◽  
Hematopoietic Stem

Objectives: T cells and interleukin 17 (IL17) have been shown to be critical in the development of hypertension (HTN). This implicates a significant role of IL17 producing T helper 17 (Th17) cells in HTN. Thus, the objective of our study was to investigate if Th17 cell levels in the peripheral blood (PB) and the bone marrow (BM) are correlated with blood pressure. Methods: Saline or Ang II was chronically infused into C57BL6 mice (1000ng Ang II/kg/min using osmotic pumps) for 3 weeks. This resulted in an increase in MAP of 45±10 mmHg. BM and PB from saline and Ang II-treated mice were analyzed using FACS. A parallel human study was conducted using blood samples obtained from hypertensive patients (n = 8, systolic BP ≥125 mmHg) and normotensive subjects (n = 10, systolic BP <125 mmHg). FACS analysis was used to examine changes in the inflammatory cells levels in these patients. Results: We observed 87% and 36% increases in both Sca-1 + c-Kit + Lin - hematopoietic stem cell (HSC; 0.23±0.04% vs. 0.43±0.05%) and Sca-1 + c-Kit - Lin - lymphoid progenitors (10.8±1.1% vs. 14.7±2.9%) in the BM of Ang II infused mice. These are upstream stem/progenitor cells for T cells. This was associated with 30% and 190% increases in CD4 + IL17 + Th17 cells in the BM and PB (1.20±0.09% vs. 1.61±0.19 % and 4.8±2.0 % vs. 14.7±3.8 % respectively) in the Ang II infused mice. Importantly, there were 58% and 206% increases of angiotensin II type 1 receptor (AT1R) expressing CD4 + T cells in the BM and PB of Ang II HTN mice (0.40±0.04 % vs. 0.63±0.14 % and 1.1±0.2 % vs 3.4±1.1 % respectively) and ~ 85% of these cells were also positive for IL-17. Consistent with mouse data, analysis of PB showed a 470% increase of Th17 cells in HTN patients (0.48±0.18 % vs 2.72±1.2%). Conclusions: We observed (i) Increased hematopoietic stem/progenitor cells in Ang II HTN mice; (ii) increased Th17 cells in both HTN mice and humans and (iii) the majority of AT1R expressing CD4 + T cells was Th17 cells. Taken together, these observations indicate that Th17 cells may be an important indicator of those destined to develop HTN and suggest that these cells may represent a novel therapeutic target.

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

2016 ◽  
Vol 23 (1) ◽  
pp. 114-118 ◽  
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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