Dataset Information

Interleukin 10 and Transforming Growth Factor Beta Polymorphisms as Risk Factors for Kawasaki Disease: A Case-Control Study and Meta-Analysis.

ABSTRACT: Background:Alteration in serum expression of Transforming Growth Factor-beta (TGF-?) and IL-10 have been suggested to play a role in the pathogenesis of Kawasaki Disease (KD). Inconsistent reports exist on the association of IL-10 polymorphisms with KD susceptibility and Coronary Artery Aneurysms (CAA). Methods:A number of 110 paediatric patients with KD and 140 healthy individuals were recruited to investigate the frequency of Single Nucleotide Polymorphisms (SNPs) of TGF-? C/T at codon 10 (rs1982073), C/G at codon 25 (rs1800471) and IL-10 A/G at -1082 (rs1800896), C/T at -819 (rs1800871) and A/C at -592 (rs1800872) and their respective genotype and haplotypes. A comprehensive search was performed in MEDLINE and SCOPUS using the keywords of interleukin 10, transforming growth factor beta, and Kawasaki disease. Moreover, previous studies investigating the TGF-? and IL-10 polymorphisms in KD were evaluated. Review Manager Version 5.1 Software was used to perform meta-analysis. Results:There was no significant association between allelic or genotypic variants in the mentioned polymorphisms in TGF-? or IL-10 with KD or CAA. The only significant haplotypic variant was TC variant at codon 10, and 25 of TGF-? polymorphisms were associated with higher risk of KD. Meta-analysis of a total number of 770 patients vs. 1471 healthy controls showed no difference in the frequency of any of the IL-10 genetic variants in KD patients, regardless of the presence of CAA. Conclusion:Polymorphisms of TGF-? or IL-10 are not associated with additional risk for KD in Iranian population. IL-10 polymorphisms at -1082, -819 and -592 positions are not associated with KD, nor do they predict coronary artery aneurysm formation.

SUBMITTER: Rahmani F

PROVIDER: S-EPMC6925396 | biostudies-literature | 2019 Oct-Dec

REPOSITORIES: biostudies-literature

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Interleukin 10 and Transforming Growth Factor Beta Polymorphisms as Risk Factors for Kawasaki Disease: A Case-Control Study and Meta-Analysis.

Rahmani Farzaneh F Ziaee Vahid V Assari Raheleh R Sadr Maryam M Rezaei Arezou A Sadr Zeinab Z Raeeskarami Seyed Reza SR Moradinejad Mohammad Hassan MH Aghighi Yahya Y Rezaei Nima N

Avicenna journal of medical biotechnology 20191001 4

<h4>Background</h4>Alteration in serum expression of Transforming Growth Factor-beta (TGF-β) and IL-10 have been suggested to play a role in the pathogenesis of Kawasaki Disease (KD). Inconsistent reports exist on the association of IL-10 polymorphisms with KD susceptibility and Coronary Artery Aneurysms (CAA).<h4>Methods</h4>A number of 110 paediatric patients with KD and 140 healthy individuals were recruited to investigate the frequency of Single Nucleotide Polymorphisms (SNPs) of TGF-β C/T a ...[more]

PMID: 31908741

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Project description:Inhibitory cytokines, such as transforming growth factor-β (TGF-β) and interleukin-10 (IL-10), are humoral factors involved in the suppressive function of regulatory T cells and play critical roles in maintaining immune homeostasis. However, TGF-β and IL-10 also have pleiotropic effects and induce humoral immune responses depending on conditions, and thus their therapeutic application to autoimmune diseases remains limited. Here, we show that a combination of TGF-β and IL-10, but not single cytokine, is required to suppress B cell activation induced by toll-like receptor (TLR) stimulation. In in vivo analyses, the simultaneous presence of TGF-β and IL-10 effectively suppressed TLR-mediated antigen-specific immune responses and ameliorated pathologies in imiquimod (TLR7 agonist)-induced lupus model and lupus-prone MRL/lpr mice. Intriguingly, TGF-β and IL-10 synergistically modulated transcriptional programs and suppressed cellular energetics of both glycolysis and oxidative phosphorylation via inhibition of the mammalian target of rapamycin complex 1 (mTORC1)/S6 kinase 1 (S6K1) pathway in TLR-stimulated B cells. On the other hand, enhancement of mTOR signaling and mitochondrial biosynthesis in TLR-stimulated B cells counteracted the synergistic inhibitory effects. The inhibitory cytokine synergy of TGF-β and IL-10 via suppression of energy metabolism was also observed in human TLR-stimulated B cells. There is increasing evidence supporting the importance of adequate metabolic signals in various immune cells to exert their immune function. In this study, we have shown that a previously unrecognized synergy of inhibitory cytokines regulates systemic humoral immune responses via modulating immunometabolism in B cells. Our findings indicate that inhibition of B cell metabolism mediated by two synergistic cytokines contributes to the induction of immune tolerance and could be a new therapeutic strategy for autoimmune diseases such as systemic lupus erythematosus.

Dataset Information

Interleukin 10 and Transforming Growth Factor Beta Polymorphisms as Risk Factors for Kawasaki Disease: A Case-Control Study and Meta-Analysis.

Publications

Interleukin 10 and Transforming Growth Factor Beta Polymorphisms as Risk Factors for Kawasaki Disease: A Case-Control Study and Meta-Analysis.

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