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

Passos, Giordani Rodrigues dos; Sato, Douglas Kazutoshi; Becker, Jéfferson; Fujihara, Kazuo

doi:10.1155/2016/5314541

Cited by 96 publications

(73 citation statements)

References 117 publications

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“…The Th17-Treg balance is impaired in PBC (Fenoglio et al 2012). Th17 cells mainly secrete IL-17, IL-6, and IL-23 and have been associated with the pathologies of several autoimmune diseases, including multiple sclerosis, rheumatoid arthritis (RA), and inflammatory bowel disease (Miao et al 2014;Alunno et al 2015;Ueno et al 2015;Dos Passos et al 2016). Patients with PBC have greater numbers of IL-17+ cells than healthy controls, and immune dysregulation in PBC is related to preferential activation of Th17 cells (Lan (Kleinewietfeld and Hafler 2013).…”

Section: Discussionmentioning

confidence: 99%

Lower Plasma Levels of IL-35 in Patients with Primary Biliary Cirrhosis

Huang

Liu

et al. 2018

Tohoku J. Exp. Med.

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Primary biliary cirrhosis (PBC) is an autoimmune liver disease. Its histological characteristics, such as progressive intrahepatic bile duct destruction, cholestasis, and liver cirrhosis, are caused by the body's autoimmune disorders. Interleukin (IL)-35 has two subunits (p35 and Ebi3) and is a member of the IL-12 family of heterodimeric cytokines. IL-35 has immunosuppressive functions and plays an important role in many autoimmune diseases. In this study, we compared plasma levels of IL-35 and relative mRNA expression levels of p35 and Ebi3 in peripheral blood mononuclear cells (PBMCs) from 70 PBC patients and 70 healthy individuals. The results showed that the relative expression levels of Ebi3 mRNA were lower in PBMCs from PBC patients than in PBMCs from healthy individuals, whereas the levels of p35 mRNA were similar in both groups. Plasma IL-35 concentrations were lower in patients with PBC than in healthy individuals. Plasma levels were higher in PBC patients at an advanced stage compared to patients at an early stage. Variable plasma levels with different stages were also found in transforming growth factor beta (TGF-β), which is mainly produced by regulatory T cells (Tregs). IL-35 and TGF-β levels were positively correlated with each other, and IL-35 was capable of promoting the inhibitory functions of Tregs in PBC patients at both the early and late stages of disease. Lower plasma IL-35 levels were accompanied by higher levels of typical clinical parameters, such as alkaline phosphatase, or of proinflammatory cytokines, such as interferon-gamma (IFN-γ), in PBC patients (P < 0.05 for each). We propose that IL-35 may be involved in the pathogenesis of PBC and could be a potential biomarker for diagnosing this disease.

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Section: Discussionmentioning

confidence: 99%

Lower Plasma Levels of IL-35 in Patients with Primary Biliary Cirrhosis

Huang

Liu

et al. 2018

Tohoku J. Exp. Med.

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“…Together, monocytes, Th1 and Th17 cells orchestrate a chronic pro-inflammatory and pro-fibrotic response to cardiovascular risk factors, leading to pathological cardiac hypertrophy, myocardial fibrosis and diastolic impairment. Thus, HFpEF is associated with hallmarks of Th1/Th17-cell mediated autoimmune diseases, such as multiple sclerosis [22,23] and type I diabetes mellitus [24,25]. This overarching theory reconciles the epidemiological associations between systemic inflammation and aging and provides a genetic basis that explains why not all aging, hypertensive patients develop HFpEF.…”

Section: Introductionmentioning

confidence: 99%

Immune Dysregulation in HFpEF: A Target for Mesenchymal Stem/Stromal Cell Therapy

Sava

Pepine

March

2020

JCM

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Over 26 million people worldwide suffer from heart failure, a disease associated with a 1 year mortality rate of 22%. Half of these patients present heart failure with preserved ejection fraction (HFpEF), for which there is no available therapy to improve prognosis. HFpEF is strongly associated with aging, inflammation, and comorbid burden, which are thought to play causal roles in disease development. Mesenchymal stromal/stem cells (MSCs) have potent immunomodulatory actions and promote tissue healing, thus representing an attractive therapeutic option in HFpEF. In this review, we summarize recent data suggesting that a two-hit model of immune dysregulation lies at the heart of the HFpEF. A first hit is represented by genetic mutations associated with clonal hematopoiesis of indeterminate potential (CHIP), which skew immune cells toward a pro-inflammatory phenotype, are associated with HFpEF development in animal models, and with immune dysregulation and risk of HF hospitalization in patients. A second hit is induced by cardiovascular risk factors, which cause subclinical cardiac dysfunction and production of danger signals. In mice, these attract proinflammatory macrophages, Th1 and Th17 cells into the myocardium, where they are required for the development of HFpEF. MSCs have been shown to reduce the pro-inflammatory activity of immune cell types involved in murine HFpEF in vitro, and to reduce myocardial fibrosis and improve diastolic function in vivo, thus they may efficiently target immune dysregulation in HFpEF and stop disease progression.

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“…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 [18].…”

Section: Relationship Withth1th2 and Tregmentioning

confidence: 99%

Role of Th17 Cells in Tumor Immunity: A Double Edged Sword

Wang¹,

Chen²

2017

dtssehs

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Objectives: Th17 cells are another CD4+T cell group after the discovery of the Th1, Th2 cell subsets, which can secrete IL-17A and Il-6. Th17 cells play a role in autoimmunity， inflammation and maintaining immune stability. Seldom studies are about the role of Th17 in tumor, research progress of Th17 cells in tumor immunity was described in this paper. Methods: we search the latest research in the world related to progress of Th17 cells in internet, and describe the progress of Th17 cells in tumor immunity. Results：The role of Th17 cells in tumor immune response is diverse. Some researchers have found that Th17 plays an anti-tumor immune response, while in other studies. Th17 cells play the opposite role. The role of Th17 cells in the local tumor seems to have two sides. Conclusions: The role of Th17 in tumor immunity is not very clear until now. Conflict idea exists in research reports. Are Th17 cells exerting regulatory roles in tumor site like Treg cells? It remains to be explored further. With more scientists in the field of Th17 research, the role of Th17 cells in tumor immunity will be further revealed.

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

Cited by 96 publications

References 117 publications

Lower Plasma Levels of IL-35 in Patients with Primary Biliary Cirrhosis

Lower Plasma Levels of IL-35 in Patients with Primary Biliary Cirrhosis

Immune Dysregulation in HFpEF: A Target for Mesenchymal Stem/Stromal Cell Therapy

Role of Th17 Cells in Tumor Immunity: A Double Edged Sword

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