The Balance of Th17 versus Treg Cells in Autoimmunity

Lee, Gap Ryol

doi:10.3390/ijms19030730

Cited by 580 publications

(487 citation statements)

References 125 publications

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“…62 Other studies showed that Foxp3 + T cells could lose Antigen-4 and Foxp3. 30 A study of rejection after transplantation indicated that 1,25(OH) 2 D 3 30 A study of rejection after transplantation indicated that 1,25(OH) 2 D 3…”

Section: Discussionmentioning

confidence: 99%

“…64 According to Fawaz et al, 63 vitamin D reduced the expression of Th17 markers and secretion of the pro-inflammatory cytokines IL-17A and Interferon-γ. 30 for Treg cells transform into Th17 cells in an inflammatory environment is a real concern because these phenotypes have the potential to exacerbate the condition. 30 for Treg cells transform into Th17 cells in an inflammatory environment is a real concern because these phenotypes have the potential to exacerbate the condition.…”

Section: Discussionmentioning

confidence: 99%

“…29 There are many adjustment mechanisms for Treg/Th17 balance, and factors such as IL-1β, tumor growth factor-β (TGF-β), costimulatory signals, histone deacetylase inhibitor, the IL-7/ IL-7R signaling pathway, and IgE factor may all play roles in RPL by increasing inflammatory Th17 cells or reducing Treg cells. [30][31][32] The regulation of a novel immunomodulator, vitamin D, on Treg/ Th17 balance has attracted researchers' attention. Vitamin D, which plays a key physiological role in critical functions of calcium and phosphorus metabolism, is synthesized in the skin and taken from food.…”

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confidence: 99%

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The role and mechanism of vitamin D‐mediated regulation of Treg/Th17 balance in recurrent pregnancy loss

Zhai

Zhou

et al. 2019

American J Rep Immunol

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Problem Vitamin D has a pivotal role in regulating immune responses in women with recurrent pregnancy loss (RPL), but the underlying mechanism has not been completely clarified. This study aimed to determine the correlation between vitamin D and Treg/Th17 and the effects of vitamin D supplementation on Treg/Th17 balance in RPL patients. Methods of study The level of vitamin D was determined in women with normal pregnancy and RPL by electrochemiluminescence. The percentages of CD4+Foxp3+ Treg, CD4+IL‐17+ Th17, and CD4+Foxp3+IL‐17+ T cells were determined by flow cytometry before and after vitamin D supplementation. Changes about Treg/Th17 balance after culturing with active vitamin D in vitro were determined. Vitamin D metabolic activity of peripheral blood mononuclear cells was also detected by RT‐PCR. Results Compared with normal pregnancy, both the level of vitamin D and the Treg/Th17 ratio were significantly decreased in women with RPL. There was a positive correlation between the level of vitamin D and the Treg/Th17 ratio in the RPL group. Within the RPL group, those who received 2 months of vitamin D supplementation showed a significantly increased Treg/Th17 ratio compared with those without vitamin D supplementation. In vitro analysis showed that adding different concentrations of active vitamin D increased the Treg/Th17 ratio, also the mRNA levels of the vitamin D receptor and the metabolic enzyme CYP24A1 increased significantly. Conclusion The occurrence of RPL may be related to vitamin D insufficiency and Treg/Th17 imbalance. The Treg/Th17 imbalance seen in women with RPL can be restored by vitamin D supplementation both in vivo and in vitro. The effects of vitamin D on the immune regulation of RPL indicate that vitamin D might be used as an alternative therapy in the future.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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The role and mechanism of vitamin D‐mediated regulation of Treg/Th17 balance in recurrent pregnancy loss

Zhai

Zhou

et al. 2019

American J Rep Immunol

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“…Th17 cells produce the signature cytokines interleukin‐17 (IL‐17), and to a lesser extent tumor necrosis factor‐α (TNF‐α), IL‐23, and IL‐6. IL‐17 can also stimulate macrophages to produce inflammatory cytokines, such as IL‐6, TNF‐ a, and IL‐1b . Zhu et al demonstrated that IL‐17 not only promotes the production of large amounts of vWF by vascular endothelial cells, but also induces apoptosis of vascular endothelial cells through the mitochondrial pathway.…”

Section: Discussionmentioning

confidence: 99%

Intensive statin treatment ameliorate the Th17/Treg functional imbalance in patients with non‐ST elevation acute coronary syndrome underwent percutaneous coronary intervention

Liu

Teng

et al. 2019

Clinical Cardiology

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Background Inflammation plays important roles in the pathogenesis of acute coronary syndrome (ACS). Statins exert positive effects on the plaque stabilization through anti‐inflammation, however, the detailed mechanism is still under investigation. Hypothesis Studies suggest that the Th17/Treg functional imbalance takes key part in the plaque destabilization and the onset of ACS. We hypothesized that intensive statin therapy could ameliorate the Th17/Treg imbalance in patients with ACS. Methods Sixty‐six patients with non‐ST elevation acute coronary syndrome (NSTE‐ACS) were randomized to conventional group and intensive group. Peripheral blood samples were collected on admission and after atorvastatin treatment. The frequencies of circulating Th17 cells and Treg cells, the levels of cytokines associated with Th17 cells (IL‐17, IL‐6 and IL‐23) and associated with Treg cells (IL‐10 and TGF‐β1) were measured through flow cytometry and ELISA assay respectively. Results One week after therapy, the frequencies of circulating Th17 cells of both the groups decreased and the frequencies of circulating Treg cells increased significantly, compared with the basal levels. Furthermore, the decreased frequencies of circulating Th17 cells and the increased frequencies of circulating Treg cells in the intensive group were significantly higher than those in the conventional group. In consistence, the decreased accumulation of IL‐17, IL‐6 and IL‐23 (cytokines relevant to Th17 cells) and the increased accumulation of IL‐10 and TGF‐β1 in peripheral blood were displayed in both groups. The changes are more significant in the intensive group. Conclusion Intensive statins therapy could ameliorate the Th17 and Treg functional imbalance in patients with ACS.

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“…REFERENCES:[1] Miyakis S, et al J Thromb Haemost. 2006;4(2):295-306[2] Sciascia S, et al Thromb Haemost.…”

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Fri0186 hydroxychloroquine on the Top of Standard Treatment With Low Dose Aspirin and Low Molecular Weight Heparin Significantly Reduces the Probability of Pregnancy Morbidity in Women With Multiple Positivity for Anti-Phospholipid Antibodies

Chighizola

Pregnolato

Bartoli

et al. 2019

Poster Presentations

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Background:Hydroxychloroquine is an anti-malarial drug that not only exerts immunomodulatory and anti-thrombotic properties, but also has been shown to reverse several effects mediated by anti-phospholipid antibodies (aPL) in models of obstetric anti-phospholipid syndrome (APS). Not surprisingly, HCQ, whose prescription during gestation is perfectly safe, has been proposed as an additional therapeutic tool in obstetric APS, but evidence of ist efficacy is still scant.Objectives:This study investigates how treatment with HCQ, prescribed in different combinations with low-dose aspirin (LDASA) and low-molecular weight heparin (LMWH), affects the probability of pregnancy morbidity (PPM).Methods:Data on pregnancies in women with persistent aPL positivity at any titre, with or without autoimmune diseases, were retrospectively collected at a single centre.A weigthed generalized estimated equation (GEE) model was applied to quantify the effect of treatment with HCQ on PPM, allowing to: i) evaluate pregnancy outcomes over time using available longitudinal data; ii) account that pregnancies of the same woman are not independent events; iii) consider that women had a different number of pregnancies; iv) estimate the role of several confounders and predictors.The model envisaged as dependent variable pregnancy outcome as a binary outcome, defined for each pregnancy as “obstetric complication yes versus no” (pregnancy loss before 10 weeks, pregnancy loss after 10 weeks, premature birth before 34 weeks, according to updated APS classification criteria).Results:Three-hundred-eighty-one women were recruited in this study: 155 women with aPL positivity (100 women with positivity for criteria aPL and 55 women with low titer aPL) and 226 women with autoimmune diseases but negative aPL. Data were collected on 847 pregnancies: 458 in women with positive aPL (172 in women with criteria aPL and 286 in women with low titer aPL) and 389 in women with autoimmune disease and negative aPL.PPM in untreated patients are presented in Table 1. Table 2 reports PPM in women receiving LDASA+/- HCQ, LDASA + LMWH +/- HCQ.Conclusion:HCQ, when added to LDASA or on the top of standard treatment with LDASA and LMWH, allows to reduce PPM. Most importantly, HCQ plus the combo LMWH + LDASA leads to a significantly reduction of PPM even in women at highest risk, namely those with multiple criteria aPL positivity.References:[1] Miyakis S, et al. J Thromb Haemost. 2006;4(2):295-306[2] Sciascia S, et al. Thromb Haemost. 2016;115(2):285-90.[3] Ruffatti A, et al. Thromb Haemost. 2018;118(4):639-646.Table 1Probabilities of PPM in untreated women with or without aPL.PPM aPL negative 38% (29-48) Low titer single aPL positivity 62% (52-71) Low titer double aPL positivity 83% (75-89) Criteria single aPL positivity 80% (71-87) Criteria multiple aPL positivity 89% (81-94)Data are expressed as PPM (95% confidence interval).Table 2 Probabilities of PPM in treated women with aPL. LDASA LDASA + HCQ LDASA + LMWH LDASA + LMWH + HCQ Low titer single aPL positivity 31%(23...

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The Balance of Th17 versus Treg Cells in Autoimmunity

Cited by 580 publications

References 125 publications

The role and mechanism of vitamin D‐mediated regulation of Treg/Th17 balance in recurrent pregnancy loss

The role and mechanism of vitamin D‐mediated regulation of Treg/Th17 balance in recurrent pregnancy loss

Intensive statin treatment ameliorate the Th17/Treg functional imbalance in patients with non‐ST elevation acute coronary syndrome underwent percutaneous coronary intervention

Fri0186 hydroxychloroquine on the Top of Standard Treatment With Low Dose Aspirin and Low Molecular Weight Heparin Significantly Reduces the Probability of Pregnancy Morbidity in Women With Multiple Positivity for Anti-Phospholipid Antibodies

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