Changes and significance of histone acetylation associated with forkhead box P3 gene during the acute phase of Kawasaki disease
10.3760/cma.j.issn.2095-428X.2018.09.005
- VernacularTitle:急性期川崎病叉头框蛋白基因组蛋白乙酰化改变的意义
- Author:
Tengfei QI
1
;
Qin WANG
;
Guobing WANG
;
Pengqiang WEN
;
Mingguo XU
;
Cong LIU
;
Yunsheng CHEN
;
Chengrong LI
Author Information
1. 遵义医学院珠海校区
- Keywords:
Kawasaki disease;
Foxp3;
Histone;
Acetylation;
Immune
- From:
Chinese Journal of Applied Clinical Pediatrics
2018;33(9):668-672
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the histone acetylation status of forkhead box P3(Foxp3)gene and its roles in immunological pathogenesis of Kawasaki disease(KD). Methods Forty - two children with KD and 32 age -matched healthy children consented to participate in this study as a control group. Co - immunoprecipitation and real -time PCR were performed to determine acetylation levels of histone H4 associated with Foxp3 gene and binding abilities of Kruppel like factor 10(KLF10)and p300 / CBP - associated factor (PCAF)with Foxp3 gene in CD4 + T cells. The proportion of CD4 + CD25 high Foxp3 + cells (Treg)and protein levels of Foxp3,KLF10,PCAF,phosphated SMAD family member 2 / 3(pSmad2 / 3)and itchy E3 ubiquitin protein ligase(Itch)were analyzed by flow cytometry. Quantitative real - time PCR was used to evaluate the levels of Foxp3,transforming growth factor - β1 receptor Ⅱ (TGF - βRⅡ), transforming growth factor - β1 receptor Ⅰ(TGF - βR Ⅰ),tyrosine kinase 2 (Tyk2),SH2 domain - containing protein - tyrosine phosphatase - 2(SHP2)and cytotoxic T - lymphocyte - associated protein 4 (CTLA4)mRNA in Treg. Plasma concentrations of TGF - β and interleukin - 6(IL - 6)were measured by enzyme - linked immunosorbent assay. Results (1)Compared with the control group,the proportion of Treg,expression levels of Foxp3 and TGF - β, and histone acetylation levels of Foxp3 promoter decreased remarkably during acute KD,and the differences were all statistically significant(all P < 0. 05),and restored after IVIG therapy(all P < 0. 05). Meanwhile,the 5 indexes afore-mentioned in KD patients with coronary artery lesions (KD - CAL +)were lower than those without coronary artery le-sions(KD - CAL -),and the differences were all statistically significant (all P < 0. 05). (2)Compared with the control group,protein levels of KLF10 and PCAF in Treg cells,and their binding abilities with Foxp3 gene were significantly down - regulated during acute KD,and the differences were all statistically significant(all P < 0. 05),and restored to some extent after IVIG treatment(all P < 0. 05). Positive correlations between protein levels of KLF10 and PCAF,and mRNA level of Foxp3 were detected in acute KD patients (r = 0. 47,0. 59,all P < 0. 05). Furthermore,protein levels of KLF10 and PCAF and their binding abilities with Foxp3 gene in KD - CAL + group were lower than those in KD -CAL - group,and the differences were all statistically significant(all P < 0. 05). (3)Compared with the control group, the plasma concentration of TGF - β and expressions of TGF - βRⅡ/ Ⅰ,pSmad2 / 3,Itch,CTLA4 and SHP2 in Treg were down - regulated during the acute phase of KD,and the differences were all statistically significant(all P < 0. 05), as well as plasma concentration of IL - 6 and expression its downstream molecule Tyk2 increased remarkably in patients with acute KD(all P < 0. 05). All the indexes mentioned before restored significantly after IVIG treatment (all P <0. 05). Simultaneously,the 7 former indexes in KD - CAL + group were found to be lower than those in KD - CAL -group,while 2 indexes of the latter in KD - CAL + group were higher than those in KD - CAL - group,and the differ-ences were all statistically significant(all P < 0. 05). Conclusion Histone hypoacetylation of Foxp3 promoter might be one of the important factors contributing to insufficiency and dysfunction of regulatory T cells during acute Kawasaki dis-ease.
