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.

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.

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.

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 The nuclear receptor REV-ERBα modulates Th17 cell-mediated autoimmune disease

2019 ◽  
Vol 116 (37) ◽  
pp. 18528-18536 ◽  
Author(s):  
Christina Chang ◽  
Chin-San Loo ◽  
Xuan Zhao ◽  
Laura A. Solt ◽  
Yuqiong Liang ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Nuclear Receptor ◽  
Th17 Cells ◽  
Inflammatory Responses ◽  
Retinoic Acid Receptor ◽  
Nuclear Hormone Receptor ◽  
Interleukin 17 ◽  
Orphan Nuclear Receptor ◽  
T Helper 17 ◽  
Autoimmune Encephalomyelitis

T helper 17 (Th17) cells produce interleukin-17 (IL-17) cytokines and drive inflammatory responses in autoimmune diseases such as multiple sclerosis. The differentiation of Th17 cells is dependent on the retinoic acid receptor-related orphan nuclear receptor RORγt. Here, we identify REV-ERBα (encoded byNr1d1), a member of the nuclear hormone receptor family, as a transcriptional repressor that antagonizes RORγt function in Th17 cells. REV-ERBα binds to ROR response elements (RORE) in Th17 cells and inhibits the expression of RORγt-dependent genes includingIl17aandIl17f. Furthermore, elevated REV-ERBα expression or treatment with a synthetic REV-ERB agonist significantly delays the onset and impedes the progression of experimental autoimmune encephalomyelitis (EAE). These results suggest that modulating REV-ERBα activity may be used to manipulate Th17 cells in autoimmune diseases.

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.

scholarly journals Interleukin 17 receptor E identifies heterogeneous T helper 17 cells in peritoneal fluid of severe endometriosis patients

2021 ◽  
Author(s):  
Yanping Jiang ◽  
Lu Wang ◽  
Yaqin Peng ◽  
Jian Qin ◽  
Aili Tan ◽  
...  
Keyword(s):  
Peritoneal Fluid ◽  
Th17 Cells ◽  
Molecular Mechanisms ◽  
Interleukin 17 ◽  
Inflammatory Disorder ◽  
T Helper ◽  
T Helper 17 ◽  
Chronic Inflammatory Disorder ◽  
Gm Csf ◽  
Metabolic Heterogeneity

Endometriosis is a chronic inflammatory disorder resulting in pelvic pain and infertility. The role of T helper 17 (Th17) cells in endometriosis remains elusive. In this study, through detecting CXCR3, CCR4, CCR10, CCR6, interleukin-17 Receptor E (IL-17RE), and CD27, live RORγt-and-IL-17A-expressing Th17 cells were distinguished and sorted from peritoneal fluid (PF) of patients with stage III and IV endometriosis. Furthermore, we found that IL-17RE and CD27 were the labels of heterogeneous PF Th17 subsets, i.e. IL-17RE-CD27- subset, IL-17RE+CD27- subset, and IL-17RE+CD27+ subset. The former two subsets expressed higher IL-17A, GM-CSF, and IL-22 and were more proliferative than the latter subset. RNA-Seq analysis on IL-17RE+ Th17 subset and IL-17RE- Th17 subset revealed up-regulation of genes involved in oxidative phosphorylation and electron transport chain in IL-17RE+ Th17 subset relative to IL-17RE- Th17 subset. Consistently, the IL-17RE+ Th17 subset produced more adenosine triphosphate (ATP) and reactive oxygen species (ROS) than IL-17RE- Th17 subset. In conclusion, this study provides a novel method to detect and isolate live PF Th17 cells from endometriosis patients and unveils the functional and metabolic heterogeneity of PF Th17 subsets. Therefore, it sheds light on the elucidation of molecular mechanisms that modulate the function of pathological Th17 cells in endometriosis.

The Abundance of Clostridium Hathewayi, a Potent Inducer of T Helper 17 (Th17) Cells, is Associated with the Disease Severity of Crohn's Disease

2017 ◽  
Vol 152 (5) ◽  
pp. S993 ◽  
Author(s):  
Kyohei Nishino ◽  
Hirotsugu Imaeda ◽  
Shigeki Sakai ◽  
Masashi Ohno ◽  
Atsushi Nishida ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Severity ◽  
Th17 Cells ◽  
T Helper ◽  
T Helper 17 ◽  
Potent Inducer
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