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PubMed | Jinan University, Keio University, Central South University, University of California at Davis and Changsha Blood Center
Type: | Journal: Scientific reports | Year: 2016

Follicular helper T cells (Tfh) have been well documented to play a critical role in autoimmunity, such as systemic lupus erythematosus (SLE), by helping B cells. In this study, high salt (sodium chloride, NaCl), under physiological conditions, was demonstrated to increase the differentiation of Tfh. A high-salt diet markedly increased lupus features in MRL/lpr mice. The mechanism is NaCl-induced DNA demethylation via the recruitment of the hydroxytransferase Ten-Eleven Translocation 2 (TET2). Gene silencing of TET2 obviously diminished NaCl-induced Tfh cell polarization in vitro. In addition, the gene expression of sh2d1a, map3k1, spn and stat5b was enhanced after NaCl treatment, consistent with the findings in lupus CD4(+)T cells. However, only spn was directly regulated by TET2, and spn was not the sole target for NaCl. Our findings not only explain the epigenetic mechanisms of high-salt induced autoimmunity but also provide an attractive molecular target for intervention strategies of patients.


PubMed | Red Cross, Xiamen Blood Center, Shaanxi Blood Center, CapitalBio Corporation and 22 more.
Type: Journal Article | Journal: PloS one | Year: 2015

Allogeneic hematopoietic stem cell transplantation is a widely used and effective therapy for hematopoietic malignant diseases and numerous other disorders. High-resolution human leukocyte antigen (HLA) haplotype frequency distributions not only facilitate individual donor searches but also determine the probability with which a particular patient can find HLA-matched donors in a registry. The frequencies of the HLA-A, -B, -C, -DRB1, and -DQB1 alleles and haplotypes were estimated among 169,995 Chinese volunteers using the sequencing-based typing (SBT) method. Totals of 191 HLA-A, 244 HLA-B, 146 HLA-C, 143 HLA-DRB1 and 47 HLA-DQB1 alleles were observed, which accounted for 6.98%, 7.06%, 6.46%, 9.11% and 7.91%, respectively, of the alleles in each locus in the world (IMGT 3.16 Release, Apr. 2014). Among the 100 most common haplotypes from the 169,995 individuals, nine distinct haplotypes displayed significant regionally specific distributions. Among these, three were predominant in the South China region (i.e., the 20th, 31st, and 81sthaplotypes), another three were predominant in the Southwest China region (i.e., the 68th, 79th, and 95th haplotypes), one was predominant in the South and Southwest China regions (the 18th haplotype), one was relatively common in the Northeast and North China regions (the 94th haplotype), and one was common in the Northeast, North and Northwest China (the 40th haplotype). In conclusion, this is the first to analyze high-resolution HLA diversities across the entire country of China, based on a detailed and complete data set that covered 31 provinces, autonomous regions, and municipalities. Specifically, we also evaluated the HLA matching probabilities within and between geographic regions and analyzed the regional differences in the HLA diversities in China. We believe that the data presented in this study might be useful for unrelated HLA-matched donor searches, donor registry planning, population genetic studies, and anthropogenesis studies.


PubMed | Soochow University of China, Sun Yat Sen University and Changsha Blood Center
Type: Letter | Journal: FEBS letters | Year: 2016

F-box proteins play pivotal roles in multiple cellular processes; however, little is known about their functions in glioma progression. In this study, we found that expression of the F-box and leucine-rich repeat protein 18 (FBXL18) is significantly upregulated in glioma tissues. Depletion of FBXL18 in glioma cells suppresses proliferation and anchorage-independent cell growth, and promotes apoptosis. We also demonstrate that depletion of FBXL18 significantly inhibits Akt activity and the phosphorylation of FOXO3a, which leads to upregulation of BCL2L11. Further mechanistic analyses indicate that FBXL18 promotes the K63-linked ubiquitination of Akt, which is required for its activation. Taken together, our results suggest that FBXL18 plays an oncogenic role through promoting K63-linked ubiquitination of Akt in glioma.


Yang Y.,Central South University | Tang Q.,Central South University | Zhao M.,Central South University | Liang G.,Central South University | And 8 more authors.
Clinical Immunology | Year: 2015

Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease involving multiple organs and characterized by overproduction of autoantibodies and T and B cell abnormalities. The treatment for SLE has been restricted to immunosuppressants and corticosteroids. Mycophenolate mofetil (MMF), as a relatively new immunosuppressant, is now widely used in the treatment of SLE patients, particularly those with nephritis. However, it is unclear whether mycophenolic acid (MPA) could modulate the reported disorders of epigenetic status in CD4+T cells from SLE patients. In this study, we demonstrated that MPA can upregulate the histone H3/H4 global acetylation status by regulating HATs and HDACs in lupus CD4+T cells. Furthermore, we found that MPA also affected the histone H4 acetylation and histone H3K4 tri-methylation levels in CD40L promoter region that inhibited the expression of CD40L. These findings indicate the potential epigenetic mechanism of therapeutic effects of MPA in SLE. © 2015 Elsevier Inc.


Tang Q.,Central South University | Yang Y.,Central South University | Zhao M.,Central South University | Liang G.,Central South University | And 8 more authors.
Lupus | Year: 2015

Background: Mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), is a noncompetitive inhibitor of inosine monophosphate dehydrogenase, and is now widely used for the treatment of systemic lupus erythematosus (SLE). Dysregulated expression of microRNA has been reported to be associated with the pathogenesis of SLE. However, it is unexplored whether altering microRNA expression in SLE patients is one of the therapeutic effects of MPA. Objectives: This study thus aims to investigate the effect of MPA on microRNAs expression in lupus CD4+T cells and its underlying mechanisms. Results: According to our microarray data, 101 upregulated microRNAs and 77 downregulated microRNAs were identified in MPA-treated lupus CD4+T cells. Among these microRNAs, miR-142-3p/5p and miR-146a expression was found to be significantly increased in MPAtreated lupus CD4+T cells compared to untreated controls. Furthermore, we observed that MPA-treated CD4+T cells from patients with SLE showed enriched levels of H4 acetylation in the putative miRNA-142 regulatory region and enhanced levels of H3 acetylation in the putative miRNA-146a regulatory region compared to untreated cells. Conclusion: Data from this study suggest that MPA activates miR-142 and miR-146a expression through histone modification at the promoter region, which may partially explain the pharmacological mechanisms of MPA for SLE. © The Author(s), 2015.


PubMed | University of Hong Kong, Jinan University, Central South University and Changsha Blood Center
Type: Journal Article | Journal: Lupus | Year: 2015

Mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), is a noncompetitive inhibitor of inosine monophosphate dehydrogenase, and is now widely used for the treatment of systemic lupus erythematosus (SLE). Dysregulated expression of microRNA has been reported to be associated with the pathogenesis of SLE. However, it is unexplored whether altering microRNA expression in SLE patients is one of the therapeutic effects of MPA.This study thus aims to investigate the effect of MPA on microRNAs expression in lupus CD4(+)T cells and its underlying mechanisms.According to our microarray data, 101 upregulated microRNAs and 77 downregulated microRNAs were identified in MPA-treated lupus CD4(+)T cells. Among these microRNAs, miR-142-3p/5p and miR-146a expression was found to be significantly increased in MPA-treated lupus CD4(+)T cells compared to untreated controls. Furthermore, we observed that MPA-treated CD4(+)T cells from patients with SLE showed enriched levels of H4 acetylation in the putative miRNA-142 regulatory region and enhanced levels of H3 acetylation in the putative miRNA-146a regulatory region compared to untreated cells.Data from this study suggest that MPA activates miR-142 and miR-146a expression through histone modification at the promoter region, which may partially explain the pharmacological mechanisms of MPA for SLE.


PubMed | University of Hong Kong, Jinan University, Central South University and Changsha Blood Center
Type: Journal Article | Journal: Clinical immunology (Orlando, Fla.) | Year: 2015

Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease involving multiple organs and characterized by overproduction of autoantibodies and T and B cell abnormalities. The treatment for SLE has been restricted to immunosuppressants and corticosteroids. Mycophenolate mofetil (MMF), as a relatively new immunosuppressant, is now widely used in the treatment of SLE patients, particularly those with nephritis. However, it is unclear whether mycophenolic acid (MPA) could modulate the reported disorders of epigenetic status in CD4(+)T cells from SLE patients. In this study, we demonstrated that MPA can upregulate the histone H3/H4 global acetylation status by regulating HATs and HDACs in lupus CD4(+)T cells. Furthermore, we found that MPA also affected the histone H4 acetylation and histone H3K4 tri-methylation levels in CD40L promoter region that inhibited the expression of CD40L. These findings indicate the potential epigenetic mechanism of therapeutic effects of MPA in SLE.


PubMed | General Hospital of Guangzhou Military Command, University of Hong Kong, Central South University and Changsha Blood Center
Type: | Journal: Clinical immunology (Orlando, Fla.) | Year: 2016

Increased circulating follicular helper-like T cells (cTfh) are reported in systemic lupus erythematosus (SLE) patients. However, whether B-cell lymphoma 6 (Bcl-6) is expressed in cTfh cells remains to be clarified. In this study, we found that the frequencies of CD4


PubMed | Capital Medical University, Arthus Biosystems, Central South University, SkyWorld and Changsha Blood Center
Type: Journal Article | Journal: BMC research notes | Year: 2016

S-Adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) are relevant to a variety of diseases. Previous reports that quantified SAM and SAH were based on HPLC or LC-MS/MS. No antibody against SAM has been generated, and the antibody against SAH cannot be used with blood samples. Immunoassays have not been used to measure SAM and SAH. In this study, ELISA was used to measure blood SAM and SAH levels.Specific antibodies against SAM were produced for the first time using a stable analog as the antigen. The monoclonal antibodies against SAM and SAH were characterized. No cross-reactivity was detected for the analyzed analogs. For the anti-SAM antibodies, the ELISA sensitivity was ~2nM, and the affinity was 7.2910It is possible to generate antibodies against active small biomolecules with weak immunogenicity, such as SAM and SAH, using traditional hybridoma technology. The antigens and antibodies described here will contribute to the development of immunoassays to measure SAM, SAH and related molecules. These assays enable the MI to be measured specifically, accurately, easily and quickly without costly equipment. This preliminary study indicates that the MI could be an effective indicator of general health, except under conditions that may alter the value of the MI, such as special diets and medications.


Xie Y.,Changsha Blood Center | Wang S.,Changsha Blood Center | Zuo Z.,Changsha Blood Center | Zhang G.,Changsha Blood Center | And 2 more authors.
International Journal of Immunogenetics | Year: 2013

Summary: This article describes a novel HLA-B*27 allele, HLA-B*27:79, which was identified in a Hunan Han ethnic individual of China by a PCR sequence-based typing method. The new sequence has one nucleotide mutation at position 437(A→T) compared with the allele B*27:04:01. This nucleotide change causes an amino acid substitution from Aspartate (Asp) to Valine (Val) at codon 122. This is the first report of mutation at this position in the HLA-B locus. Then, we investigated the HLA-B*27 subtype polymorphism of the Hunan Han population, and the results showed that B*27:04, B*27:05 and B*27:06 are the predominant subtypes with the allele frequencies 0.97%, 0.26% and 0.10% respectively. © 2013 John Wiley & Sons Ltd.

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