Article
Immunology
Chloe D. Goldsmith, Thomasina Donovan, Nicole Vlahovich, David B. Pyne
Summary: This perspective article discusses how exercise can delay T cell ageing by analyzing the relationship between metabolism and epigenetics, proposing a potential impact of exercise on CD4+ T cell plasticity.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Pharmacology & Pharmacy
Huihui Chen, Chongqing Tan, Zhiruo Wang, Jie Zha, Hong Liu, Zheng Dong, Guochun Chen
Summary: Long-term glucocorticoid (GC) treatment induces persistent lymphopenia in patients with primary glomerular disease, and GCs continuously suppress CD4+ T cells even after dose tapering, leading to decreased CD4/CD8 ratio and impaired CD4+ T cell biology. GCs alter FOXP3 expression and promote an active T regulatory (Treg) cell phenotype with enhanced IL-10 production. Mechanistically, GCs disrupt mTORC1 pathway transcriptional regulation and targeting mTORC1 signaling can modify the viability of GC-exposed CD4+ T cells. DNA methylation changes in mTORC1 pathway genes contribute to the long-term influence of GC on CD4+ T cell biology.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Nutrition & Dietetics
Hui Lin, Yiran Zhao, Yajie Zhu, Cheng Li, Wei Xu, Xi Chen, Hefeng Huang, Li Jin
Summary: This study suggests that high-fat diet during pregnancy may lead to exacerbated allergic asthma in offspring through the activation and proliferation of CD4(+) T-cells. Similar effects were observed in humans, with an increased risk of developing allergic diseases at 3 years old.
Review
Cell Biology
Xiaomin Ma, Xin Wang, Guangbing Zheng, Guiqin Tan, Fangyu Zhou, Wenwen Wei, Dan Tian, Hongsong Yu
Summary: Behçet's disease is a chronic multisystem autoimmune disease with complex pathogenesis involving genetics, environmental factors, and gut microbiota. Previous studies have indicated that external environmental factors and abnormalities in epigenetic modification may impact the development of BD.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Immunology
Marco Kunzli, David Masopust
Summary: This review provides updates on our understanding of the biology of memory CD4(+) T cells as well as key technological advances that facilitate their characterization.
Article
Cell Biology
Xiaofan Lu, Yann-Alexandre Vano, Xiaoping Su, Alexandra Helleux, Veronique Lindner, Roger Mouawad, Jean-Philippe Spano, Morgan Roupret, Eva Comperat, Virginie Verkarre, Cheng-Ming Sun, Mostefa Bennamoun, Herve Lang, Philippe Barthelemy, Wenxuan Cheng, Irwin Davidson, Fangrong Yan, Wolf Herve Fridman, Catherine Sautes-Fridman, Stephane Oudard, Gabriel G. Malouf
Summary: In this study, we integrated epigenetic and transcriptome data to identify a ccRCC subtype characterized by cancer-specific promoter hypermethylation and epigenetic silencing of Polycomb targets. We developed and validated an index of methylation-based epigenetic silencing (iMES) that predicts primary resistance to immune checkpoint inhibition in ccRCC patients. High iMES is associated with VEGF pathway silencing, endothelial cell depletion, immune activation/suppression, EZH2 activation, BAP1/SETD2 deficiency, and resistance to immune checkpoint inhibitors. Combination therapy with hypomethylating agents or tyrosine kinase inhibitors may benefit patients with high iMES. Intriguingly, tumors with low iMES exhibit increased endothelial cells and improved immune checkpoint inhibitor response, suggesting the importance of angiogenesis in immune checkpoint inhibitor treatment. We also developed a transcriptome-based analogous system for extended applicability of iMES. Our study highlights the interaction between epigenetic alterations and tumor microenvironment in determining immunotherapy response.
CELL REPORTS MEDICINE
(2023)
Article
Oncology
Lien Provez, Tom Putteman, Mattias Landfors, Juliette Roels, Lindy Reunes, Sara T'Sas, Wouter Van Loocke, Beatrice Lintermans, Stien De Coninck, Morgan Thenoz, Wouter Sleeckx, Natalia Mackowska-Maslak, Tom Taghon, Marc R. Mansour, Nadine Farah, Koen Norga, Peter Vandenberghe, Rishi S. Kotecha, Steven Goossens, Sofie Degerman, Renate De Smedt, Pieter Van Vlierberghe
Summary: T-cell lymphoblastic lymphoma (T-LBL) is a rare and aggressive lymphatic cancer, often diagnosed in teenagers and young adults. Patients are usually treated with chemotherapy or hematopoietic stem cell transplantation, but relapse still occurs. Decitabine, a DNA hypomethylating agent, shows potential as a less toxic therapy. This study provides preclinical proof of the use of decitabine as a therapeutic agent in T-LBL.
Article
Medicine, Research & Experimental
Xiaofei Gao, Yang Song, Jiali Wu, Shuang Lu, Xiaoli Min, Limin Liu, Longyuan Hu, Meiling Zheng, Pei Du, Yaqin Yu, Hai Long, Haijing Wu, Sujie Jia, Di Yu, Qianjin Lu, Ming Zhao
Summary: Iron plays an important role in regulating pathogenic T cell differentiation and autoantibody production in SLE. High-iron diet promotes Tfh cell expansion, and the miR-21/BDH2 axis may be critical for iron accumulation during Tfh cell differentiation.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Immunology
Ali Mustafa, Coit Patrick, Amr H. Sawalha
Summary: Differential DNA methylation of CD4+ T cells was found between male and female patients with SLE, suggesting potential mechanisms underlying the gender difference in disease severity and activation of T cell pathways.
CLINICAL IMMUNOLOGY
(2022)
Article
Agriculture, Dairy & Animal Science
Yiming Yuan, Gang Zheng, Zhen You, Lulu Wang, Ziyi Wang, Congjiao Sun, Changjun Liu, Xianyao Li, Peng Zhao, Yongqiang Wang, Ning Yang, Ling Lian
Summary: This study used whole genome bisulfite sequencing (WGBS) and RNA-seq to identify genes playing important roles in the tumor transformation of Marek's disease (MD). 8 genes, including CD4 and HMGB1, were found to be negatively correlated with methylation and showed high expression in the MDV-infected group. Overexpression of CD4 and HMGB1 significantly promoted MDCC-MSB-1 cell proliferation, suggesting their potential promoting roles in MD tumorigenesis.
Article
Multidisciplinary Sciences
Rana Falahat, Anders Berglund, Ryan M. Putney, Patricio Perez-Villarroel, Shota Aoyama, Shari Pilon-Thomas, Glen N. Barber, James J. Mule
Summary: The lack or loss of tumor antigenicity is a key mechanism of immune evasion and resistance to T cell-based immunotherapies. Epigenetic regulation, specifically DNA methylation, plays a role in suppressing the STING signaling function in melanoma cells, but this suppression can be reversed through pharmacologic DNA methylation inhibition. Restoring STING signaling improves melanoma cell antigenicity and enhances recognition and killing by cytotoxic T cells, highlighting the functional significance of epigenetic processes in tumor-immune evasion.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Gastroenterology & Hepatology
Jazib Uddin, Sunil Tomar, Ankit Sharma, Lisa Waggoner, Varsha Ganesan, Sahiti Marella, Yanfen Yang, Taeko Noah, Simone Vanoni, Andrew Patterson, Chang Zeng, Paul S. Foster, Rodney Newberry, Shrinivas Bishu, John Y. Kao, Michael J. Rosen, Lee Denson, Philip D. King, Kasper Hoebe, Senad Divanovic, Ariel Munitz, Simon P. Hogan
Summary: The inhibitory receptor PIR-B plays a role in regulating CD4(+) IL17a(+) T-cell pathogenic memory responses, modulating chronic intestinal inflammatory responses and the development of colitis. The downstream axis involving PIR-B, Src-homology region 2 domain-containing phosphatase-1/2, and mammalian target of rapamycin complex 1 signaling is important for CD4(+) IL17a(+) cell survival. Furthermore, transcriptional signatures associated with Th17 cells and tissue resident memory networks were enriched in PIR-B+ murine CD4(+) T cells and human CD4(+) T cells expressing LILRB3, demonstrating the potential significance of PIR-B and its human homologue in inflammatory diseases.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Immunology
Suhas Sureshchandra, Norma Mendoza, Allen Jankeel, Randall M. Wilson, Nicole E. Marshall, Ilhem Messaoudi
Summary: Maternal obesity has been shown to disrupt fetal immune system development and increase susceptibility to infection in offspring. Offspring of obese mothers show higher frequencies of memory CD4 T cells, potential signs of in vivo activation, and possible functional defects. These abnormalities are associated with genomic changes and may explain the link between the obesogenic maternal environment and fetal immune reprogramming.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Shuo Li, Weihua Zeng, Xiaohui Ni, Qiao Liu, Wenyuan Li, Mary L. Stackpole, Yonggang Zhou, Arjan Gower, Kostyantyn Krysan, Preeti Ahuja, David S. Lu, Steven S. Raman, William Hsu, Denise R. Aberle, Clara E. Magyar, Samuel W. French, Steven -Huy B. Han, Edward B. Garon, Vatche G. Agopian, Wing Hung Wong, Steven M. Dubinett, Xianghong Jasmine Zhoua
Summary: Plasma cell-free DNA (cfDNA) is a noninvasive biomarker that can be used to detect abnormal cell death due to diseases. By establishing a comprehensive tissue methylation atlas and utilizing the cfSort deep-learning model, the performance of tissue deconvolution in cfDNA can be significantly improved, enabling disease detection and longitudinal treatment monitoring.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Immunology
Anthony M. Joudi, Carla P. Reyes Flores, Benjamin D. Singer
Summary: FoxP3(+) regulatory T cells play a crucial role in maintaining immune homeostasis, self-tolerance, and resolving inflammation and tissue damage. However, their plasticity in inflammatory microenvironments could lead to loss of function and contribute to inflammatory pathology, presenting a barrier to Treg cell immunotherapy. Understanding the determinants of Treg cell stability and utilizing epigenetic mechanisms could enhance the efficacy and minimize toxicity of Treg cell-based therapeutics.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Ophthalmology
Ao Lu, Zhangluxi Liu, Guannan Su, Peizeng Yang
Summary: This cross-sectional bibliometric analysis provides an overview of global uveitis research in the last decade, including countries/regions, organizations, scholars, journals, trending topics, and fundings. The USA is the leading country in uveitis study, while Asian countries/regions like China and India play a substantial role. Trendy topics include biologics, COVID-19, and OCTA.
OCULAR IMMUNOLOGY AND INFLAMMATION
(2023)
Article
Ophthalmology
Xiaotang Wang, Qi Zhang, Shengping Hou, Jian Qi, Liping Du, Fuzhen Li, Qingfeng Cao, Peizeng Yang
Summary: The polymorphisms in PTPN6 and LncRNA C1RL-AS1 genes are associated with ocular BD in Han Chinese patients. The rs4013722 polymorphism of LncRNA C1RL-AS1 confers susceptibility to ocular BD, which is influenced by sex. The gene polymorphisms of PTPN6 are not associated with BD patients.
OCULAR IMMUNOLOGY AND INFLAMMATION
(2023)
Article
Ophthalmology
Suo Guo, Hui Liu, Yu Gao, Lingyu Dai, Jing Xu, Peizeng Yang
Summary: This study investigated vascular changes of fundus in quiescent Behcet uveitis (BU) using widefield swept source optical coherence tomography angiography and fluorescein angiography. The results showed that patients with BU had enlargement of foveal avascular zone and decreased vessel density within a 300 μm width around the foveal avascular zone in both superficial and deep retina. Furthermore, BU patients had lower vessel density of choriocapillaris in the peripheral fundus compared to controls. The combination of swept source optical coherence tomography angiography with fluorescein angiography accurately evaluated the changes in the retinal and choroidal vasculature in BU.
RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
(2023)
Article
Rheumatology
Jiayu Meng, Na Li, Xianyang Liu, Shengjun Qiao, Qian Zhou, Jun Tan, Ting Zhang, Zhifang Dong, Xiaopeng Qi, Aize Kijlstra, Liming Mao, Peizeng Yang, Shengping Hou
Summary: The study reveals that NLRP3 plays an anti-inflammatory role in experimental autoimmune encephalomyelitis and experimental autoimmune uveitis. It inhibits AIM2 inflammasome-mediated uveitis by regulating the p-SIK1/SREBF1 pathway.
ARTHRITIS & RHEUMATOLOGY
(2023)
Article
Immunology
Wanyun Zhang, Zhijun Chen, Kun Yi, Guannan Su, Yaning Liu, Yang Deng, Yinan Zhang, Qingfeng Cao, Yanlin Pu, Xiang Luo, Yujie Lai, Peizeng Yang
Summary: In this study, the researchers discovered that DNA 5-hmC and the TET2 gene play an important role in the development of Vogt-Koyanagi-Harada (VKH) disease. They found that the levels of DNA 5-hmC and TET activity were elevated in CD4+ T cells from active VKH patients, and identified 6 candidate target genes involved in the development of VKH disease. Functional experiments showed that TET2 up-regulated the expression of LRRC39, which in turn influenced Th1/Treg responses in CD4+ T cells. This study provides new insights into the pathogenesis of VKH and a potential target for epigenetic therapy.
CLINICAL IMMUNOLOGY
(2023)
Article
Immunology
Yunyun Zhu, Qiuyue Yu, Guannan Su, Na Shao, Jie Feng, Xiang Luo, Chunjiang Zhou, Peizeng Yang
Summary: This study investigated the mechanism of recombinant interferon-alpha 2a (IFN alpha 2a) in the treatment of Behcet's uveitis (BU) and found that IFN alpha 2a exerts its effects by modulating the function of dendritic cells (DCs) and CD4+ T cells.
CLINICAL IMMUNOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Xu Gao, Peizeng Yang, Cunliang Zhang, Deyang Kong, Yuefei Ji, Junhe Lu
Summary: This study reveals that nitrophenolic compounds can be formed by the reaction of natural organic matter and nitrite under sunlight. This suggests that the natural contribution of these compounds in the environment may have been overlooked.
ENVIRONMENTAL CHEMISTRY LETTERS
(2023)
Article
Ophthalmology
Jiankang Shan, Lin Li, Liping Du, Peizeng Yang
Summary: This study aimed to determine whether single nucleotide polymorphisms (SNPs) in the TBX21 gene are associated with susceptibility to acute anterior uveitis (AAU) in a Chinese population. The results showed no significant association between two candidate SNPs (rs4794067, rs11657479) in the TBX21 gene and AAU susceptibility. Stratification analysis and haplotype analysis also did not reveal any significant differences or associations. Therefore, the polymorphisms rs4794067 and rs11657479 in the TBX21 gene do not confer disease susceptibility to AAU in the Chinese population.
EXPERIMENTAL EYE RESEARCH
(2023)
Article
Ophthalmology
Tingting Zhao, Qingfeng Cao, Chunjiang Zhou, Yao Wang, Liping Du, Peizeng Yang
Summary: This study found that the HLA-DRB1 * 04:05 and DQB1 * 04:01 alleles, as well as the DRB1 * 04:05-DQB1 * 04:01 haplotype, could be potential risk factors for SO.
OCULAR IMMUNOLOGY AND INFLAMMATION
(2023)
Article
Chemistry, Multidisciplinary
Ruonan Li, Jiangyi Liu, Ping Yi, Xianli Yang, Jun Chen, Chenyang Zhao, Xingyun Liao, Xiaotang Wang, Zongren Xu, Huiping Lu, Hongshun Li, Zhi Zhang, Xianyang Liu, Junjie Xiang, Ke Hu, Hongbo Qi, Jia Yu, Peizeng Yang, Shengping Hou
Summary: Through single-cell RNA sequencing and single-cell assay for transposase-accessible chromatin sequencing, the heterogeneity of retinal progenitor cells and their differentiation into seven major types of retinal cells is explored. Lineage-determining transcription factors are identified and their regulatory networks at the transcriptomic and epigenomic levels are refined. Treatment with the inhibitor of RE1 silencing transcription factor, X5050, induces more neurogenesis and reduces Muller glial cells. The signatures of major retinal cells and their correlation with pathogenic genes associated with ocular diseases are described, providing an integrated framework for exploring the single-cell developmental dynamics of the human primary retina.
Editorial Material
Cell Biology
Yiguo Qiu, Xianli Shen, Heping Xu
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Ophthalmology
Guannan Su, Liping Du, Hongsong Yu, Minghui Li, Ruocheng Huang, Xiaonan Yang, Detao Wang, Qing Wang, Peizeng Yang
Summary: We conducted a genome-wide methylation association analysis of VKH disease by studying 60 VKH patients and 60 healthy controls. We identified aberrant CpG sites in both HLA and non-HLA gene regions that were associated with VKH disease. The mRNA levels of certain genes were found to be increased in VKH patients, consistent with the hypomethylated CpG status in those gene regions. Additionally, seven aberrantly methylated CpG sites were identified as potential diagnostic markers for VKH disease.
EXPERIMENTAL EYE RESEARCH
(2023)
Article
Immunology
Guiqin Tan, Guangbing Zheng, Jiang Li, Yingping Zhu, Zhongzhi Liang, Hua Li, Hongsong Yu, Xin Wang
Summary: The study investigated the association of FoxP3 gene polymorphisms with Graves' disease in a Southwest Chinese Han population. The findings suggest that FoxP3/rs3761548 is significantly associated with female GD patients in this population.
IMMUNITY INFLAMMATION AND DISEASE
(2023)
Article
Ophthalmology
Qingyan Jiang, Qingfeng Wang, Shiyao Tan, Jinyu Cai, Xingsheng Ye, Guannan Su, Peizeng Yang
Summary: This study explored the potential role of plasma-derived exosomal microRNAs (miRNAs) in the development of regulatory T cell (Treg)/T helper 17 (Th17) cell imbalances in Behcet's uveitis (BU). Exosomes from patients with active BU promoted Th17 cell differentiation and inhibited Treg cell differentiation. Highly expressed miR-19b-3p induced a Treg/Th17 cell imbalance, probably by downregulating CD46 expression, and its inhibition restored the Treg/Th17 cell balance in CD4+T cells from patients with active BU.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2023)
Article
Genetics & Heredity
Chunya Zhou, Shiya Cai, Yuhong Xie, Zhen Zeng, Jun Zhang, Guannan Su, Qiuying Wu, Xingsheng Ye, Qingfeng Cao, Peizeng Yang, Jianmin Hu
Summary: This study revealed an association between PRKCD rs74437127 and CARD9 rs3812555 polymorphisms and VKH susceptibility, and showed that the increased susceptibility of rs3812555 for VKH may be mediated by regulating CARD9 gene expression and the production of pro-inflammatory cytokines, such as TNF-alpha.
