Peizeng Yang

Chongqing Medical University, Ch’ung-ch’ing-shih, Chongqing Shi, China

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Publications (142)472.77 Total impact

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    ABSTRACT: This study aimed to investigate the role of genetic variants including single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) of TBX21, GATA3, Rorc and Foxp3 genes in Behcet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome in a Chinese Han population. Genotyping of 25 SNPs was performed by iPLEX system (Sequenom) or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). TaqMan real time PCR was used to assess CNVs. The expression of Rorc and Foxp3 were examined by real-time PCR and cytokine production was measured by ELISA. High Rorc CNV was associated with the susceptibility to BD (P = 8.99 × 10(-8), OR = 3.0), and low Foxp3 CNV predisposed to BD in female patients (P = 1.92 × 10(-5), OR = 3.1). CNVs for the investigated genes were not altered in VKH syndrome. Further functional studies demonstrated that the relative mRNA expression levels of Rorc were increased in individuals with high Rorc copy number, but not for Foxp3. Increased production of IL-1β and IL-6 was found in individuals carrying a high CNV of Rorc. Our study showed that high CNVs of Rorc and low CNVs of Foxp3 confer risk for BD but not for VKH syndrome. The tested 25 SNPs in TBX21, GATA3, Rorc and Foxp3 did not associate with BD and VKH syndrome.
    Scientific Reports 04/2015; 5:9511. DOI:10.1038/srep09511 · 5.08 Impact Factor
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    ABSTRACT: Bach2 was reported to play a key role in T lymphocyte development and maturation to mediate immunological homeostasis. Several autoimmune and immune-related diseases were shown to be associated with Bach2 gene polymorphisms. The current study was designed to explore the association between Bach2 gene polymorphism with Vogt-Koyanagi-Harada (VKH) syndrome and Behcet's disease (BD) in a Chinese Han population. -427 patients with BD, 422 patients with VKH and 623 controls were recruited for the first stage from a Chinese Han population. The second stage included another set of 388 patients with BD and 460 healthy subjects. PCR fragment length polymorphism methodology was used for genotyping. Frequencies of genotypes and alleles were measured by direct counting and compared between cases and controls by χ(2) test. No difference could be detected between patients suffering from BD or VKH with healthy controls concerning allele and genotype frequencies of rs11755527, rs3757247, rs12212193 and rs2474619. Although in the first stage the frequencies of genotype CC and AC of rs2474619 showed a weak statistical difference between BD and the control group (Pc=0.02), the difference was lost after the second stage and combined stage experiment. The investigated Bach2 gene polymorphisms (rs11755527, rs3757247, rs12212193 and rs2474619) are not related to the susceptibility to either VKH or BD in our investigated Chinese Han population. This project was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR-CCC-12002184). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    The British journal of ophthalmology 04/2015; DOI:10.1136/bjophthalmol-2014-306163 · 2.81 Impact Factor
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    ABSTRACT: Conbercept (KH902), a novel recombinant, soluble vascular endothelial growth factor (VEGF) receptor-IgG fusion protein, has been developed as a new drug for ocular neovascularization and macular edema. The present study aims to clarify the changes in conbercept levels, VEGF, and intraocular pressure (IOP) after the intravitreal injection of conbercept into diabetic mouse eyes. Five-week-old C57BL/6 mice were injected with streptozotocin to induce diabetes. Total VEGF and conbercept levels in the eyes were detected using an ELISA kit at -2 h, 1 h, 1 d, 4 d, 8 d, 16 d, 28 d, and 34 d after intravitreal injection of conbercept into diabetic and control mice. IOP was measured with a noninvasive TonoLab tonometer 7 d after intravitreal conbercept injection. The concentration of conbercept in the treated eyes increased immediately after injection and remained at high levels for 4 d (29.77±27.19 ng/ml, 20.28±28.85 ng/ml, and 42.43±36.51 ng/ml for days 1, 2, and 4, respectively). The concentration of conbercept in the untreated fellow eyes increased from day 2 to day 4 after injection with a level of about 1% of that in the injected eyes. Conbercept concentrations in both the treated and fellow eyes decreased from day 7 after intravitreal injection. The concentration of VEGF in the treated eyes increased significantly 1 h after injection when compared with the baseline measured 2 h before injection in both the diabetic and control mice (645.91±86.47 pg/ml versus 296.10±76.11 pg/ml and 860.50±201.47 pg/ml versus 377.69±70.72 pg/ml, respectively). VEGF concentration reached its peak 24 h after injection and then decreased thereafter. At day 7 after intravitreal injection, the difference in IOP between mice that received conbercept and mice that received PBS injections was not significant (p>0.05). Conbercept and total VEGF levels in the mouse eyes were elevated after intravitreal injection of conbercept. Increased VEGF levels likely reflect VEGF sequestered by conbercept. These data could be helpful in understanding the metabolism of anti-VEGF drugs in the eye and for determining the protocol of multiple intravitreal injections of conbercept in patients.
    Molecular vision 02/2015; 21:185-93. · 2.25 Impact Factor
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    ABSTRACT: Purpose: To test whether gene copy number variations(CNVs) of TLRs are associated with uveitis. Methods: CNVs of the TLRs were detected by Real-time PCR. The first stage study comprised 400 Behcet's disease(BD) patients, 400 VKH syndrome patients, 400 acute anterior uveitis associated with or without ankylosing spondylitis patients and 600 healthy subjects. The second stage included another set of 578 BD patients and 1000 healthy controls. The frequencies of TLR gene copy number types (TLR1,TLR2,TLR3,TLR5,TLR6,TLR7,TLR9, TLR10), were compared between patients and controls using the χ2 test. Real-Time PCR was used to detect mRNA expression from PBMCs obtained from healthy controls following stimulation with the TLR7 agonist R848. Levels of TNF-α, IL-6 and IL-1β in culture supernatants were measured by ELISA. Results: All TLRs tested except TLR7 had a gene copy number of 2 in more than 98% of individuals tested. In the first stage study, we found a significantly increased frequency of >1 copy of TLR7(located on the X chromosome) in male BD patients and >2 copies in female patients(Pc=0.021; Pc=0.048, respectively). A second stage and combined study confirmed the association (PC=1.14×10-6, PC=9.12×10-5, respectively). TLR7 mRNA expression in PBMCs was increased in male healthy carriers having >1 copy of TLR7 or females having >2 copies following stimulation with R848(P=0.021, P=0.006, respectively). No effect of the various TLR7 copies on the release of TNF-α, IL-6 and IL-1β could be detected. Conclusions: This study provides evidence that a high copy number of TLR7 confers risk for BD in a Chinese Han population. Copyright © 2015 by Association for Research in Vision and Ophthalmology.
    Investigative Ophthalmology &amp Visual Science 02/2015; DOI:10.1167/iovs.14-15030 · 3.66 Impact Factor
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    ABSTRACT: Vogt-Koyanagi-Harada (VKH) syndrome and Behcet's disease (BD) are two common form of uveitis in China. The aim of this study was to investigate the association of C-type lectin domain family 16, member A (CLEC16A) gene polymorphisms with Vogt-Koyanagi-Harada syndrome and Behcet's disease in a Chinese Han population. A two-stage association study was carried out in 988 VKH syndrome patients,400 BD patients and 976 healthy controls. Eight single nucleotide polymorphisms of CLEC16A gene were determined with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The data were analyzed by χ(2) test or Fisher's exact test and corrected for multiple comparisons by the Bonferroni method. The first stage study showed that the frequency of the A allele of rs6498169 was significantly decreased in VKH syndrome patients (Pc = 1.1 × 10(-2), OR = 0.7, 95%CI = 0.6-0.9). No significant association was observed in the other 7 SNPs between VKH syndrome patients and controls. No association was found with BD for the 8 SNPs tested. We further confirmed the association of single nucleotide polymorphism rs6498169 with VKH syndrome in another cohort. Consistent with the first stage study, the combined study showed significantly lower frequencies of the AA genotype and the A allele of rs6498169 in VKH syndrome patients (Pc = 3.5 × 10(-4), OR = 0.6, 95%CI = 0.5-0.7; Pc = 8.2 × 10(-4), OR = 0.8, 95%CI = 0.7-0.9, respectively). In conclusion, the study suggested that a CLEC16A polymorphism may be protective against VKH syndrome in a Chinese Han population. Copyright © 2015. Published by Elsevier Ltd.
    Experimental Eye Research 01/2015; 132. DOI:10.1016/j.exer.2015.01.004 · 3.02 Impact Factor
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    ABSTRACT: Purpose: Recent studies have shown that a decrease of regulatory T (Treg) cells may contribute to the activity of acute anterior uveitis (AAU) and ankylosing spondylitis (AS). A number of immunogenetic factors including IL2RA, miR-27a, miR-182 and FoxO1 are associated with Treg cell function. In this study, we investigated the association between polymorphisms of these genes and AAU with or without AS in a Chinese Han population. Methods: Using PCR-RFLP assay, a two-stage association study was performed in 680 AAU patients with or without AS and 1280 controls. Gene expression was quantified by real-time PCR. Results: In the first stage study, an association analysis of 10 single nucleotide polymorphisms (SNPs) was performed in 230 AAU patients with AS, 240 AAU patients without AS and 650 controls. The results showed significantly increased frequencies of the FoxO1/rs2297626 AA genotype and A allele in AAU patients with AS (AA genotype: P =6.23×10-5, OR=1.86; A allele: P =2.17×10-4, OR=1.53). No significant association of the other 9 SNPs with AAU with or without AS was observed. In the second stage study, an association analysis of FoxO1/rs2297626 was performed in 210 AAU patients with AS and 630 controls. The second stage and combined studies confirmed the association of FoxO1/rs2297626 with AAU with AS (AA genotype: P =3.45×10-8, OR=1.85; A allele: P =1.55×10-7, OR=1.55). Conclusions:This study suggests that FoxO1, but not miR-27a, miR-182 and IL2RA, contributes to the genetic susceptibility of AAU with AS, but none of the tested polymorphisms confer risk to AAU without AS.
    Investigative Ophthalmology &amp Visual Science 11/2014; 55(12):7970-7974. DOI:10.1167/iovs.14-15460 · 3.66 Impact Factor
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    ABSTRACT: To investigate the associations of IL17A, IL17F, IL23A, and IL23R copy number variants (CNVs) with Vogt-Koyanagi-Harada (VKH) syndrome and Behçet's disease (BD) and the possible mechanisms involved. Two-stage case-control and functional studies. A total of 1159 VKH patients, 1036 BD patients, and 2050 controls were enrolled. TaqMan real-time polymerase chain reaction assay was used for genotyping of copy number variant. Cell proliferation was measured by colorimetric assay. Association of CNVs in IL17A, IL17F, IL23A, and IL23R with BD and VKH syndrome and the functional roles of IL17F CNVs. Increased frequencies of more than 2 copies of IL17F and IL23A were found in BD patients as compared with controls (IL17F: P = 4.17 × 10(-8); odds ratio [OR], 2.2; IL23A: P = 2.86 × 10(-11); OR, 2.8, respectively). A similar result was found for VKH syndrome (IL17F: P = 2.84 × 10(-13); OR, 2.7; IL23A: P = 4.46 × 10(-17); OR, 3.4, respectively). Interestingly, the association of IL17F and IL23A with BD was found only in male patients (IL17F: P = 1.06 × 10(-6); OR, 2.3; IL23A, P = 3.81 × 10(-8); OR, 2.8, respectively), but not in female patients. No association of CNVs in IL17A and IL23R was found for BD and VKH syndrome. IL17F protein levels were correlated positively with gene copy numbers (P = 3.43 × 10(-7)). Individuals with high IL17F copies showed enhanced peripheral blood mononuclear cells (PBMC) proliferation (P = 5.67 × 10(-3)). High gene copy numbers of IL17F and IL23A were associated with BD and VKH syndrome. Enhanced IL17F protein production and PBMC proliferation were associated with high IL17F copy numbers. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
    Ophthalmology 11/2014; 122(3). DOI:10.1016/j.ophtha.2014.09.025 · 6.17 Impact Factor
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    ABSTRACT: Interleukin-37 (IL-37) is emerging as an important inhibitor of immune response. This study was set up to investigate the expression of IL-37 in Vogt-Koyanagi-Harada (VKH) disease and to explore its possible regulatory role during inflammation. Twenty-four untreated active VKH patients, 10 VKH patients receiving corticosteroids and cyclosporin A (CsA), and 35 healthy controls were included in this study. IL-37 expression in lipopolysaccharides (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) from these 3 groups was assayed by real-time polymerase chain reaction (RT-PCR) and flow cytometry. Cytokines in the supernatants of stimulated PBMCs and CD4(+) T cells were assayed by enzyme-linked immunosorbent assay (ELISA). Mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) activation were measured by flow cytometry. VKH patients showed a decreased IL-37 and IL-27 expression and increased IL-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) levels in PBMC culture supernatants. IL-37 significantly inhibited the production of IL-1β, IL-6, and TNF-α, but induced IL-27 expression. VKH patients treated with corticosteroids combined with CsA showed a regression of the intraocular inflammation, and treatment was associated with an enhanced IL-37 production. IL-37 did not affect the production of IL-17, interferon-gamma (IFN-γ), or IL-10 from CD4(+) T cells. The present study suggests that a decreased IL-37 expression in VKH patients is associated with a reduced control of the inflammatory response. Treatment of VKH patients with corticosteroids and CsA is associated with an increased expression of IL-37, which suggests that corticosteroids and CsA may partly exert their immunosuppressive effect by upregulating IL-37 production.
    Journal of Interferon & Cytokine Research 10/2014; 35(4). DOI:10.1089/jir.2014.0042 · 3.90 Impact Factor
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    ABSTRACT: Considering the phenotypical consequences and association of C4 copy number variation (CNV) with various autoimmune diseases, we aimed to examine C4 CNVs for 1027 patients with Vogt-Koyanagi-Harada (VKH) syndrome and 2083 controls.
    British Journal of Ophthalmology 09/2014; DOI:10.1136/bjophthalmol-2014-305596 · 2.81 Impact Factor
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    ABSTRACT: To identify new genetic risk factors for Vogt-Koyanagi-Harada (VKH) syndrome, we conducted a genome-wide association study of 2,208,258 SNPs in 774 cases and 2,009 controls with follow-up in a collection of 415 cases and 2,006 controls and a further collection of 349 cases and 1,588 controls from a Han Chinese population. We identified three loci associated with VKH syndrome susceptibility (IL23R-C1orf141, rs117633859, Pcombined = 3.42 × 10(-21), odds ratio (OR) = 1.82; ADO-ZNF365-EGR2, rs442309, Pcombined = 2.97 × 10(-11), OR = 1.37; and HLA-DRB1/DQA1, rs3021304, Pcombined = 1.26 × 10(-118), OR = 2.97). The five non-HLA genes were all expressed in human iris tissue. IL23R was also expressed in the ciliary body, and EGR2 was expressed in the ciliary body and choroid. The risk G allele of rs117633859 in the promoter region of IL23R exhibited low transcriptional activation in a cell-based reporter assay and was associated with diminished IL23R mRNA expression in human peripheral blood mononuclear cells.
    Nature Genetics 08/2014; 46(9):1007-11. DOI:10.1038/ng.3061 · 29.65 Impact Factor
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    ABSTRACT: Recent studies show that the aryl hydrocarbon receptor (AhR) is involved in immune responses. AhR is activated following interaction with its ligands, such as 6-formylindolo[3,2-b]carbazole (FICZ) and 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE). In this study, we investigated the role of AhR activation by its endogenous ligands in the pathogenesis of ocular Behcet's disease (BD). The expression of AhR was significantly decreased in active BD patients as compared to inactive BD patients and normal controls. Both FICZ and ITE inhibited Th1 and Th17 polarization and induced the expression of IL-22 by PBMCs and by CD4(+)T cells in active BD patients and normal controls. Stimulation of purified CD4(+)T cells with FICZ or ITE caused a decreased expression of RORC, IL-17, IL-23R, and CCR6 and an increased phosphorylation of STAT3 and STAT5. The present study suggests that a decreased AhR expression is associated with disease activity in BD patients. The activation of AhR by either FICZ or ITE was able to inhibit Th1 and Th17 cell polarization. Further studies are needed to investigate whether modulation of AhR might be used in the treatment of BD.
    Mediators of Inflammation 06/2014; 2014:195094. DOI:10.1155/2014/195094 · 2.42 Impact Factor
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    ABSTRACT: Instruction: Interleukin 27 (IL-27) is an important regulator of the proinflammatory T-cell response. In this study, we investigated its role in the pathogenesis of Behcet's disease (BD). Methods: IL-27 mRNA in peripheral blood mononuclear cells (PBMCs) was examined by performing RT-PCRs. Cytokine levels in sera or supernatants of PBMCs, naive CD4(+) T cells, dendritic cells (DCs) and DC/T cells were determined by enzyme-linked immunosorbent assay. We used RNA interference in naive CD4(+) T cells to study the role of interferon regulatory factor 8 (IRF8) in the inhibitory effect of IL-27 on Th17 cell differentiation. Flow cytometry was used to evaluate the frequency of IL-17- and interferon gamma- producing T cells. Results: The expression of IL-27p28 mRNA by PBMCs and IL-27 in the sera and supernatants of cultured PBMCs were markedly decreased in patients with active BD. A higher frequency of IL-17- producing CD4+ T (Th17) cells and increased IL-17 production under Th17 polarizing conditions were observed in patients with active BD. IL-27 significantly inhibited Th17 cell differentiation. Downregulation of IRF8 by RNA interference abrogated the suppressive effect of IL-27 on Th17 differentiation. IL-27 inhibited the production of IL-1 beta, IL-6 and IL-23, but promoted IL-10 production, by DCs. IL-27-treated DCs inhibited both the Th1 and Th17 cell responses. Conclusions: The results of the present study suggest that a decreased IL-27 expression is associated with disease activity in BD patients. Low IL-27 expression may result in a higher Th1 and Th17 cell response and thereby promote the autoinflammatory reaction observed in BD. Manipulation of IL-27 may offer a new treatment modality for this disease.
    Arthritis Research & Therapy 05/2014; 16(3):R117. DOI:10.1186/ar4570 · 4.12 Impact Factor
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    ABSTRACT: Purpose To investigate the associations of single nucleotide polymorphisms (SNPs) of three genes (IL-12B, IL-12Rβ1 and IL-12Rβ2) in Behcet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome in a Chinese Han population. Methods A total of 806 BD cases, 820 VKH patients, and 1600 healthy controls were involved in this study. The first investigation included 400 BD patients, 400 VKH cases, and 600 healthy individuals. A second confirmatory study included a separate set of 406 BD patients, 420 VKH cases and another 1000 normal controls. Genotyping was carried out by PCR-restriction fragment length polymorphism assay and results were validated by using direct sequencing. The χ2 test was performed to compare the allele and genotype frequencies between cases and healthy controls. Results This study comprised two phases. In the first phase study, a significantly increased frequency of the rs3212227/IL-12B genotype CC and C allele was found in BD patients as compared to controls (Bonferroni corrected p value (pc) = 0.009, OR 1.8; pc = 0.024, OR 1.3, respectively). Moreover, the frequency of the C allele of rs3212227/IL-12B was also significantly increased in VKH patients (pc = 0.012, OR 1.3, 95% CI 1.1 to 1.6). No associations were found for the other seven tested SNPs either in BD or VKH disease. The second study as well as the combined data confirmed the significant association of rs3212227/IL-12B with BD (CC genotype: combined pc = 6.3×10−7, OR = 1.8; C allele: combined pc = 2.0×10−5, OR = 1.3, respectively) and the C allele frequency of rs3212227/IL-12B as the risk factor to VKH patients (combined pc = 2.5×10−5, OR 1.3, 95% CI 1.2 to 1.5). Conclusions Our study revealed that the IL-12B gene is involved both in the susceptibility to BD as well as VKH syndrome.
    PLoS ONE 05/2014; 9(5):e98373. DOI:10.1371/journal.pone.0098373 · 3.53 Impact Factor
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    ABSTRACT: Protein tyrosine phosphatase non-receptor 22 (PTPN22) is a key negative regulator of T lymphocytes and has emerged as an important candidate susceptibility factor for a number of immune-related diseases. This study aimed to examine the predisposition of PTPN22 SNPs to Vogt-Koyanagi-Harada (VKH) syndrome and acute anterior uveitis (AAU) associated with ankylosing spondylitis (AS). A total of 1005 VKH syndrome, 302 AAU+AS+ patients and 2010 normal controls among the Chinese Han population were enrolled in the study. Genotyping, PTPN22 expression, cell proliferation, cytokine production and cell activation were examined by PCR-RFLP, Real-time PCR, CCK8, ELISA and Flow cytometry. The results showed significantly increased frequencies of the rs2488457 CC genotype and C allele but a decreased frequency of the GG genotype in VKH syndrome patients (PBonferroni correction (Pc) = 3.47×10-7, OR = 1.54; Pc = 3.83×10-8, OR = 1.40; Pc = 6.35×10-4, OR = 0.62; respectively). No significant association of the tested SNPs with AAU+AS+ patients was observed. Functional studies showed a decreased PTPN22 expression, impaired cell proliferation and lower production of IL-10 in rs2488457 CC cases compared to GG cases (Pc = 0.009, Pc = 0.015 and Pc = 0.048 respectively). No significant association was observed concerning T cell activation and rs2488457 genotype. The study showed that a functional variant of PTPN22 confers risk for VKH syndrome but not for AAU+AS+ in a Chinese Han population, which may be due to a modulation of the PTPN22 expression, PBMC proliferation and IL-10 production.
    PLoS ONE 05/2014; 9(5):e96943. DOI:10.1371/journal.pone.0096943 · 3.53 Impact Factor
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    ABSTRACT: Previous studies have identified miR-182, miR-27a, FoxO1, and IL2RA as regulatory factors for Treg cell development and function. In order to investigate the association of miR-182, miR-27a, FoxO1, and IL2RA gene polymorphisms with Behçet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome in a Chinese Han population, a two-stage association study was performed in 820 BD, 900 VKH patients, and 1,800 controls using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. In the first stage study, association analysis of 10 single nucleotide polymorphisms (SNPs) was performed in 400 BD, 400 VKH patients, and 600 controls. The results showed significantly decreased frequencies of the miR-182/rs76481776 CC genotype and C allele in BD (P = 3.36 × 10(-4), OR = 0.55; P = 4.74 × 10(-4), OR = 0.59) and VKH patients (P = 1.11 × 10(-4), OR = 0.53; P = 1.26 × 10(-4), OR = 0.56). No significant association of the other nine SNPs with BD or VKH was observed. In the second stage study, association analysis of miR-182/rs76481776 was performed in 420 BD, 500 VKH patients, and 1,200 controls. The second stage and combined studies confirmed the association of miR-182/rs76481776 with BD (CC genotype: P = 3.25 × 10(-7), OR = 0.58; C allele: P = 1.81 × 10(-7), OR = 0.60) and VKH (CC genotype: P = 7.89 × 10(-8), OR = 0.57; C allele: P = 2.52 × 10(-8), OR = 0.59). Real-time PCR analysis showed a significantly increased expression of miR-182 in TT/CT cases compared to CC cases in anti-CD3/CD28 antibodies-stimulated CD4(+) T cells (P = 2.1 × 10(-2)). In conclusion, this study suggests that miR-182, but not miR-27a, FoxO1, and IL2RA, contributes to the genetic susceptibility of BD and VKH. MiR-182 contributes to genetic susceptibility of BD and VKH. No significant association of miR-27a, FoxO1, and IL2RA with BD or VKH was observed. Significantly increased expression of miR-182 in TT/CT cases compared to CC cases was observed.
    Journal of Molecular Medicine 05/2014; 92(9):961-7. DOI:10.1007/s00109-014-1159-9 · 4.74 Impact Factor
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    ABSTRACT: The aim of the study was to investigate the association of TNFα-induced protein 3 interacting with protein 1 (TNIP1) gene polymorphisms with Vogt-Koyanagi-Harada (VKH) syndrome and Behcet's disease (BD) in a Han Chinese population. A total of 656 BD patients, 961 VKH syndrome patients and 1534 healthy controls were included in this two-stage case control study. Seven SNPs, including rs17728338, rs7708392, rs10036748, rs3762999, rs999556, rs4958881 and rs3792783, belonging to TNIP1 were genotyped and analyzed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The data were analyzed by using the χ2 or Fisher's exact test and corrected for multiple comparisons by the Bonferroni method. A significantly increased frequency of the GG genotype and a decreased frequency of the AG genotype of rs17728338 were found in VKH patients (Pc = 0.038 OR = 1.934, 95% CI = 1.438∼2.601). No significant difference was noted in allele or genotype frequencies of rs7708392, rs10036748, rs3762999, rs999556, rs4958881 and rs3792783, between VKH patients and healthy controls (Pc>0.05). No significant difference was noted in allele or genotype frequencies of the tested 7 SNPs between BD patients and healthy controls. Analysis of extraocular clinical findings, did not reveal an association of the TNIP1 gene polymorphisms with BD or VKH syndrome subgroups. A TNIP1 polymorphism may be a risk factor for VKH syndrome in Han Chinese.
    PLoS ONE 05/2014; 9(5):e95573. DOI:10.1371/journal.pone.0095573 · 3.53 Impact Factor
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    ABSTRACT: Purpose: To investigate whether a synthetic LXR agonist TO901317 (TO90) ameliorates ocular inflammation in experimental autoimmune uveitis (EAU) and to explore its underlying mechanism. Methods: EAU was induced with subcutaneous injection of IRBP161-180 peptide in B10.RIII mice. TO90 were administrated orally for successive 16 or 8 days as prevention or effector phase, respectively. LXRs, p65, ABCA1 and pro-inflammatory genes were detected with real-time PCR and (or) Western blotting. IRBP-specific lymphocyte proliferation was detected by MTT. Intracellular IFN-γ and IL-17 in CD4+T cells were measured by flow cytometry. Results: Both LXRα and LXRβ were expressed in mouse retina. After administrated TO90, the expression of LXRα was upregulated in the naïve mice. It was also increased in vehicle and TO90 treated EAU mice. ABCA1 was enhanced in TO90 treated naïve and EAU mice but was unchanged in vehicle treated EAU mice, suggesting activation of LXRα by TO90 is ligand dependent. Activation of LXRα decreased the expressions of proinflammatory cytokines. TO90 inhibited IRBP-specific immune responses. The proportions of Th1 and Th17 that expressing IFN-γ and IL-17 were reduced in TO90 treated EAU mice in both prevention and effector phases. TO90 significantly down-regulated the expressions of a NF-κB subunit p65. Conclusion: TO90 activates LXRα and potently attenuates ocular inflammation in EAU. Alleviation of ocular inflammation could partially result from inhibition of the NF-κB signaling pathway. TO90 reduces IFN-γ and IL-17 expressing in both prevention and treatment scenarios. Our data suggests that LXR agonist may become a novel class of therapeutic agent for autoimmune uveitis.
    Investigative ophthalmology & visual science 04/2014; 55(4). DOI:10.1167/iovs.13-13323 · 3.66 Impact Factor
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    ABSTRACT: AhR is well known for mediating the toxic effects of dioxin containing pollutants but has also been shown to be involved in the natural regulation of the immune response. In this study, we investigated the effect of AhR activation by its endogenous ligands 6-formylindolo[3,2-b]carbazole (FICZ), and 2-(1′Hindole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) on the differentiation, maturation and function of monocyte-derived DCs in Behcet's disease (BD) patients. Here, we showed that AhR activation by FICZ and ITE downregulated the expression of co-stimulatory molecules including HLA-DR, CD80 and CD86, while it had no effect on the expression of CD83 and CD40 on DCs derived from BD patients and normal controls. LPS-treated DCs from active BD patients showed a higher level of IL-1β, IL-6, IL-23 and TNF-α production. FICZ or ITE significantly inhibited the production of IL-1β, IL-6, IL-23 and TNF-α, but induced IL-10 production by DCs derived from active BD patients and normal controls. FICZ or ITE-treated DCs significantly inhibited the Th17 and Th1 cell response. Activation of AhR either by FICZ or ITE inhibits DC differentiation, maturation and function. Further studies are needed to investigate whether manipulation of the AhR pathway may be used to treat BD or other autoimmune diseases.
    Clinical & Experimental Immunology 04/2014; 177(2). DOI:10.1111/cei.12352 · 3.28 Impact Factor
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    Min Sun, Peizeng Yang, Liping Du, Yan Yang, Jian Ye
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    ABSTRACT: To explore whether IRAK1 and IRAK4 are involved in the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease. Thirty-nine VKH patients and thirty-two healthy controls were included in this study. The mRNA levels of IRAK1 and IRAK4 from active VKH patients, inactive VKH patients, and normal controls in peripheral blood mononuclear cells (PBMCs) were detected using real-time quantitative PCR. CD4+T cells were purified from PBMCs obtained from active VKH patients and normal controls. The effect of IRAK1/4 inhibition on CD4+T cell proliferation following stimulation with IL-18 or IL-1β was measured using a modified MTT assay. CD4+T cell expression of IFN-γ and IL-17 were detected by flow cytometry (FCM) and enzyme-linked immunosorbent assay (ELISA). The effect of IRAK1/4 inhibition on NF-κB, STAT1, and STAT3 activation was detected by FCM. The mRNA levels of IRAK1 and IRAK4 were both significantly increased in active VKH patients compared to inactive VKH patients and healthy controls. No difference in the IRAK1 or IRAK4 mRNA level could be detected between inactive patients and healthy controls. After incubation with IRAK1/4 inhibitor, the proliferation of CD4+T cells was inhibited both in the active VKH patients and in the healthy controls. IRAK1/4 inhibition was also associated with a decreased expression of IFN-γ and IL-17. Phosphorylation of NF-κB, STAT1, and STAT3 in CD4+T from healthy controls was significantly decreased after inhibition of IRAK1/4. High mRNA levels of IRAK1 and IRAK4 correlated with VKH disease activity. IRAK1 and IRAK4 play a role in the activation and proliferation of CD4+T cells and the higher expression observed in VKH may contribute to the pathogenesis of this blinding condition.
    PLoS ONE 04/2014; 9(4):e93214. DOI:10.1371/journal.pone.0093214 · 3.53 Impact Factor

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1k Citations
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Institutions

  • 2008–2014
    • Chongqing Medical University
      Ch’ung-ch’ing-shih, Chongqing Shi, China
  • 2005–2010
    • Sun Yat-Sen University
      • State Key Laboratory of Oncology
      Guangzhou, Guangdong Sheng, China
  • 2003
    • Oregon Health and Science University
      • Department of Cell & Developmental Biology
      Portland, Oregon, United States
  • 2000–2003
    • Sun Yat-Sen University of Medical Sciences
      中山, Guangdong, China
  • 2002
    • Zhongshan University
      中山, Guangdong, China
    • University of Amsterdam
      Amsterdamo, North Holland, Netherlands