scholarly journals Cytokines that Modulate the Differentiation of Th17 Cells in Autoimmune Uveitis

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Kailei Guo ◽  
Xiaomin Zhang
Keyword(s):  
Th17 Cells ◽  
Transforming Growth Factor ◽  
Therapeutic Targets ◽  
Transforming Growth Factor Β1 ◽  
T Helper ◽  
Immune Disease ◽  
T Helper 17 ◽  
Autoimmune Uveitis ◽  
Ifn Γ ◽  
Tgf Β1

Increasing evidence has suggested that T helper 17 (Th17) cells play a central role in the pathogenesis of ocular immune disease. The association between pathogenic Th17 cells and the development of uveitis has been confirmed in experimental and clinical studies. Several cytokines affect the initiation and stabilization of the differentiation of Th17 cells. Therefore, understanding the mechanism of related cytokines in the differentiation of Th17 cells is important for exploring the pathogenesis and the potential therapeutic targets of uveitis. This article briefly describes the structures, mechanisms, and targeted drugs of cytokines—including interleukin (IL)-6, transforming growth factor-β1 (TGF-β1), IL-1β, IL-23, IL-27, IL-35, IL-2, IL-4, IL-21, and interferon (IFN)-γ—which have an important influence on the differentiation of Th17 cells and discusses their potential as therapeutic targets for treating autoimmune uveitis.

scholarly journals Role of Vitamin D in Premature Atherosclerosis in Adolescents Type 1 Diabetes through Transforming Growth Factor-β1, Interferon-γ, Interleukin-10, and Interleukin-17

2020 ◽  
Vol 8 (B) ◽  
pp. 738-746
Author(s):  
Haryudi Aji Cahyono ◽  
Wisnu Barlianto ◽  
Dian Handayani ◽  
Handono Kalim
Keyword(s):  
Vitamin D ◽  
Type 1 Diabetes ◽  
Transforming Growth Factor ◽  
Interleukin 10 ◽  
Interferon Γ ◽  
Transforming Growth Factor Β1 ◽  
Premature Atherosclerosis ◽  
Ifn Γ ◽  
Tgf Β1

BACKGROUND: Cardiovascular disease (CVD) is one the cause of mortality in patients with type 1 diabetes (T1D). The development of CVD is mainly triggered by atherosclerosis, which is associated with the inflammatory process. AIM: The current study was aimed to investigate the association of Vitamin D level and premature atherosclerosis in adolescents with T1D, mainly through the regulation of various cytokines (interferon-γ [IFN-γ], IL-17, interleukin-10 [IL-10], and transforming growth factor-β1 [TGF-β1]). METHODS: This study was designed as a cross-sectional study involving 40 T1D and 40 healthy control who came to the outpatient clinic, Saiful Anwar Hospital, Malang, Indonesia, within the study period (January 2019-July 2019). RESULTS: Our data demonstrated that the IFN-γ and IL-17 levels were significantly higher (p < 0.001), whereas the TGF-β1 and IL-10 levels were significantly lower (p < 0.001) in T1D group compared with control. Furthermore, T1D also has higher carotid intima-media thickness (cIMT) value and lower flow-mediated dilatation (FMD) value compared to the control group (p < 0.001). Level of 25(OH)D3 was strongly associated with reduced cIMT and elevated FMD (p < 0.005). The direct effect of 25(OH)D3 on cIMT and FMD was higher than the indirect effect of Vitamin D through TGF-β1, IL-10, IL-17, and IFN-γ. The cutoff value of 25(OH)D3 levels for the risk of atherosclerosis was 12.8 ng/dL (sensitivity 85.7% and specificity 86.7%). CONCLUSION: The level of Vitamin D in the T1D group was significantly lower than those in healthy children and Vitamin D deficiency substantially influences the formation of premature atherosclerosis.

scholarly journals Treatment of Experimental (Trinitrobenzene Sulfonic Acid) Colitis by Intranasal Administration of Transforming Growth Factor (Tgf)-β1 Plasmid

2000 ◽  
Vol 192 (1) ◽  
pp. 41-52 ◽  
Author(s):  
Atsushi Kitani ◽  
Ivan J. Fuss ◽  
Kazuhiko Nakamura ◽  
Owen M. Schwartz ◽  
Takashi Usui ◽  
...  
Keyword(s):  
Growth Factor ◽  
Sulfonic Acid ◽  
Transforming Growth Factor ◽  
Intraperitoneal Administration ◽  
Experimental Colitis ◽  
Inhibitory Effect ◽  
Transforming Growth Factor Β1 ◽  
Trinitrobenzene Sulfonic Acid ◽  
Ifn Γ ◽  
Tgf Β1

In this study, we show that a single intranasal dose of a plasmid encoding active transforming growth factor β1 (pCMV-TGF-β1) prevents the development of T helper cell type 1 (Th1)-mediated experimental colitis induced by the haptenating reagent, 2,4,6-trinitrobenzene sulfonic acid (TNBS). In addition, such plasmid administration abrogates TNBS colitis after it has been established, whereas, in contrast, intraperitoneal administration of rTGF-β1 protein does not have this effect. Intranasal pCMV-TGF-β1 administration leads to the expression of TGF-β1 mRNA in the intestinal lamina propria and spleen for 2 wk, as well as the appearance of TGF-β1–producing T cells and macrophages in these tissues, and is not associated with the appearances of fibrosis. These cells cause marked suppression of interleukin (IL)-12 and interferon (IFN)-γ production and enhancement of IL-10 production; in addition, they inhibit IL-12 receptor β2 (IL-12Rβ2) chain expression. Coadministration of anti–IL-10 at the time of pCMV-TGF-β1 administration prevents the enhancement of IL-10 production and reverses the suppression of IL-12 but not IFN-γ secretion. However, anti–IL-10 leads to increased tumor necrosis factor α production, especially in established colitis. Taken together, these studies show that TGF-β1 inhibition of a Th1-mediated colitis is due to: (a) suppression of IL-12 secretion by IL-10 induction and (b) inhibition of IL-12 signaling via downregulation of IL-12Rβ2 chain expression. In addition, TGF-β1 may also have an inhibitory effect on IFN-γ transcription.

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 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.

Circulating T helper 17 and IFN-γ positive Th17 cells in Major Depressive Disorder

2020 ◽  
Vol 394 ◽  
pp. 112811
Author(s):  
Raghumoy Ghosh ◽  
PVSN Kiran Kumar ◽  
Prasenjit Mitra ◽  
Purvi Purohit ◽  
Naresh Nebhinani ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Th17 Cells ◽  
T Helper ◽  
T Helper 17 ◽  
Major Depressive ◽  
Ifn Γ

scholarly journals Interaction of Mycobacterium tuberculosis-Induced Transforming Growth Factor β1 and Interleukin-10

1999 ◽  
Vol 67 (11) ◽  
pp. 5730-5735 ◽  
Author(s):  
Catherine Othieno ◽  
Christina S. Hirsch ◽  
Beverly D. Hamilton ◽  
Katalin Wilkinson ◽  
Jerrold J. Ellner ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Growth Factor ◽  
Mononuclear Cells ◽  
Transforming Growth Factor ◽  
Interleukin 10 ◽  
Transforming Growth Factor Β1 ◽  
Ifn Γ ◽  
Tgf Β1

ABSTRACT Mycobacterium tuberculosis is associated with the activation of cytokine circuits both at sites of active tuberculosis in vivo and in cultures of mononuclear cells stimulated by M. tuberculosis or its components in vitro. Interactive stimulatory and/or inhibitory pathways are established between cytokines, which may result in potentiation or attenuation of the effects of each molecule on T-cell responses. Here we examined the interaction of transforming growth factor β1 (TGF-β1) and interleukin-10 (IL-10) in purified protein derivative (PPD)-stimulated human mononuclear cell cultures in vitro. TGF-β1 induced monocyte IL-10 (but not tumor necrosis factor alpha) production (by 70-fold, P < 0.02) and mRNA expression in the absence but not in the presence of PPD. Both exogenous recombinant (r) IL-10 and rTGF-β1 independently suppressed the production of PPD-induced gamma interferon (IFN-γ) in mononuclear cells from PPD skin test-positive individuals. Synergistic suppression of IFN-γ in cultures containing both rTGF-β1 and rIL-10 was only seen when the responder cell population were peripheral blood mononuclear cells (PBMC) and not monocyte-depleted mononuclear cells and when PBMC were pretreated with rTGF-β1 but not with rIL-10. Suppression of PPD-induced IFN-γ in PBMC containing both rTGF-β1 (1 ng/ml) and rIL-10 (100 pg/ml) was 1.5-fold higher (P< 0.05) than cultures containing TGF-β1 alone and 5.7-fold higher (P < 0.004) than cultures containing IL-10 alone. Also, neutralization of endogenous TGF-β1 and IL-10 together enhanced PPD-induced IFN-γ in PBMC in a synergistic manner. Thus, TGF-β1 and IL-10 together potentiate the downmodulatory effect on M. tuberculosis-induced T-cell production of IFN-γ, and TGF-β1 alone enhances IL-10 production. At sites of active M. tuberculosis infection, these interactions may be conducive to the suppression of mononuclear cell functions.

scholarly journals The effects of phenanthrene exposure on Treg and Th17 cells related cytokines in female rats

2020 ◽  
Vol 9 (3) ◽  
pp. 283-289
Author(s):  
Haitao Ma ◽  
Huizhen Guo ◽  
Wenwen Zhang ◽  
Fengjing Hu ◽  
Yushan Huang ◽  
...  
Keyword(s):  
Th17 Cells ◽  
Corn Oil ◽  
Treg Cells ◽  
Interferon Γ ◽  
Female Rats ◽  
Female Rat ◽  
T Helper ◽  
T Helper 17 ◽  
Immune Impairment ◽  
Ifn Γ

Abstract Phenanthrene (Phe) female rat model was established to explore the mechanism of Phe on immune impairment. The rats were randomly divided into three groups, including control (C), low (L), and high (H) groups. Phe was supplied to L and H groups at the dose of 180 and 900 mg/kg orally at first day and with the dose of 90 and 450 mg/kg by intraperitoneal injection at the last 2 days. The C group was enriched with the same volume of corn oil. The liver tissue was collected. Then, the protein and mRNA expressions of interleukin (IL)-35 and the concentration IL-17 were detected to evaluate the function of regulatory T cells (Treg cells) and T helper 17 cells (Th17 cells). In addition, IL-1β and interferon-γ (IFN-γ) were analyzed to evaluate the immune impairment. The results showed that the protein and mRNA expressions of IL-35 decreased significantly in H groups (P &lt; 0.05). Meanwhile, there were significant increases in IL-17, IFN-γ and IL-1β in the liver of H group (P &lt; 0.05). This study demonstrated that Phe exposure might be associated with the immune impairment via changing inflammatory mediators including IL-35 and IL-17 in female rats.

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.

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