scholarly journals Regulation of FoxP3+Regulatory T Cells and Th17 Cells by Retinoids

2008 ◽  
Vol 2008 ◽  
pp. 1-12 ◽  
Author(s):  
Chang H. Kim

Vitamin A has both positive and negative regulatory functions in the immune system. While vitamin A is required for normal formation of immune cells and epithelial cell barriers, vitamin A deficiency can lead to increased inflammatory responses and tissue damage. The mechanism with which vitamin A and its metabolites such as retinoids negatively regulate inflammatory responses has not been clearly defined. Recently, it has been established that retinoids promote the generation of immune-suppressive FoxP3+regulatory T cells while they suppress the T cell differentiation into inflammatory Th17 cells in the periphery such as intestine. These novel functions of retinoids provide a potentially important immune regulatory mechanism. In this review, we discuss the functions of retinoids in the development of the FoxP3+cells and Th17 cells, the phenotype and functions of retinoid-induced FoxP3+T cells, and the impact of retinoid-induced FoxP3+T cells on the immune tolerance.

2020 ◽  
Vol 117 (48) ◽  
pp. 30639-30648
Author(s):  
Dan Hu ◽  
Emily C. Tjon ◽  
Karin M. Andersson ◽  
Gabriela M. Molica ◽  
Minh C. Pham ◽  
...  

IL-17–producing Th17 cells are implicated in the pathogenesis of rheumatoid arthritis (RA) and TNF-α, a proinflammatory cytokine in the rheumatoid joint, facilitates Th17 differentiation. Anti-TNF therapy ameliorates disease in many patients with rheumatoid arthritis (RA). However, a significant proportion of patients do not respond to this therapy. The impact of anti-TNF therapy on Th17 responses in RA is not well understood. We conducted high-throughput gene expression analysis of Th17-enriched CCR6+CXCR3−CD45RA−CD4+T (CCR6+T) cells isolated from anti-TNF–treated RA patients classified as responders or nonresponders to therapy. CCR6+T cells from responders and nonresponders had distinct gene expression profiles. Proinflammatory signaling was elevated in the CCR6+T cells of nonresponders, and pathogenic Th17 signature genes were up-regulated in these cells. Gene set enrichment analysis on these signature genes identified transcription factor USF2 as their upstream regulator, which was also increased in nonresponders. Importantly, short hairpin RNA targetingUSF2in pathogenic Th17 cells led to reduced expression of proinflammatory cytokines IL-17A, IFN-γ, IL-22, and granulocyte-macrophage colony-stimulating factor (GM-CSF) as well as transcription factor T-bet. Together, our results revealed inadequate suppression of Th17 responses by anti-TNF in nonresponders, and direct targeting of the USF2-signaling pathway may be a potential therapeutic approach in the anti-TNF refractory RA.


2019 ◽  
Vol 52 ◽  
pp. 204-211 ◽  
Author(s):  
Daniel Lozano-Ojalvo ◽  
Mónica Martínez-Blanco ◽  
Leticia Pérez-Rodríguez ◽  
Elena Molina ◽  
Carmen Peláez ◽  
...  

2010 ◽  
Vol 12 (1) ◽  
pp. 86-95 ◽  
Author(s):  
Takashi Maruyama ◽  
Jun Li ◽  
Jose P Vaque ◽  
Joanne E Konkel ◽  
Weifeng Wang ◽  
...  

2018 ◽  
Vol 104 (3) ◽  
pp. 217-226 ◽  
Author(s):  

BackgroundBiannual vitamin A supplementation is a well-established survival tool for preschool children 6 months and older in vitamin A deficient populations but this schedule misses the opportunity to intervene on most young infant deaths. Randomised trials of neonatal vitamin A supplementation (NVAS) in the first few days of life to assess its impact on under 6-month mortality in low/middle-income countries have had varying results.MethodsInvestigators of 11 published randomised placebo-controlled NVAS trials (n=163 567 children) reanalysed their data according to an agreed plan and pooled the primary outcomes of mortality from supplementation through 6 and 12 months of age using random effects models and meta-regression. One investigator withdrew but allowed use of the data.FindingsOverall there was no effect of NVAS on infant survival through 6 (risk ratio (RR) 0.97; 95% CI 0.89 to 1.06) or 12 months of age (RR 1.00; 95% CI 0.93 to 1.08) but results varied by study population characteristics.NVAS significantly reduced 6-month mortality among the trials conducted in Southern Asia (RR 0.87; 95% CI 0.77 to 0.98), in contexts with moderate or severe vitamin A deficiency (defined as 10% or higher proportion of women with serum retinol <0.7 µmol/L or 5% or more women with night blindness) (RR 0.87; 95% CI 0.80 to 0.94), early infant mortality was 30 or more per 1000 live births (RR 0.91; 95% CI 0.85 to 0.98), 75% or more of infant mortality occurred in the first 6 months of life (RR 0.92; 95% CI 0.84 to 1.01), or where >32% mothers had no schooling (RR 0.88; 95% CI 0.80 to 0.96). NVAS did not reduce mortality in the first 6 months of life in trials conducted in Africa, in contexts characterised by a low prevalence of vitamin A deficiency, lower rates of infant mortality and where maternal education was more prevalent. There was a suggestion of increased infant mortality in trials conducted in Africa (RR 1.07; 95% CI 1.00 to 1.15).Individual-level characteristics such as sex, birth weight, gestational age and size, age at dosing, parity, time of breast feeding initiation, maternal education and maternal vitamin A supplementation did not modify the impact of NVAS.ConclusionNVAS reduced infant mortality in South Asia, in contexts where the prevalence of maternal vitamin A deficiency is moderate to severe and early infant mortality is high; but it had no beneficial effect on infant survival in Africa, in contexts where the prevalence of maternal vitamin A deficiency is lower, early infant mortality is low.


2018 ◽  
Vol 88 (5) ◽  
pp. e12715 ◽  
Author(s):  
Linlin Wang ◽  
Xiaocen Wang ◽  
Lin Tong ◽  
Jian Wang ◽  
Maosen Dou ◽  
...  

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