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The function and regulation of TET2 in innate immunity and inflammation

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Protein & Cell 2021年第3期12卷 165-173页

作者： Boyi Cong Qian Zhang Xuetao Cao Laboratory of Immunity and inflammation College of Life SciencesNankai UniversityTianjin 300071China National Key Laboratory of Medical immunology Institute of ImmunologyNavy Military Medical UniversityShanghai 200433China Department of immunology Center for ImmunotherapyInstitute of Basic Medical SciencesChinese Academy of Medical SciencesBeijing 100005China

TET2,a member of ten-eleven translocation(TET)family as a-ketoglutarate-and Fe2+-dependent dioxygenase catalyzing the iterative oxidation of 5-methylcytosine(5mC),has been widely recognized to be an important regulator for normal hematopoiesis especially *** and dysregulation of TET2 contribute to the development of multiple hematological *** studies reveal that TET2 also plays an important role in innate immune homeostasis by promoting DNA demethylation or independent of its enzymatic ***,we focus on the functions of TET2 in the initiation and resolution of inflammation through epigenetic regulation and signaling *** addition,we highlight regulation of TET2 at various molecular levels as well as the correlated inflammatory diseases,which will provide the insight to intervene in the pathological process caused by TET2 dysregulation.

关键词： TET2 innate immune response DNA demethylation inflammatory resolution inflammatory diseases

Direct and Indirect Role of Toll-Like Receptors in T Cell Mediated Immunity

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Cellular & Molecular immunology 2004年第4期1卷 239-246页

作者： Mousa Komai-Koma Division of immunology Infection and InflammationUniversity of GlasgowGlasgowG 6NT.UK

Toll-like receptors (TLR) are pathogen-associated molecular patterns (PAMPs) recognition receptors that play an important role in protective immunity against infection and *** act as central integrators of a wide variety of signals,responding to diverse agonists of microbial *** of Toll-like receptors by microbial products leads to signaling pathways that activate not only innate,but also adaptive immunity by APC dependent or independent *** evidence revealed that TLR signals played a determining role in the skewing of na(?)ve T cells towards either Th1 or Th2 *** of Toll-like receptors also directly or indirectly influences regulatory T cell ***,TLRs are required in both immune activation and immune *** of TLRs has significantly enhanced our understanding of innate and adaptive immune responses and provides novel therapeutic approaches against infectious and inflammatory *** & Molecular immunology.2004;1(4):239-246.

关键词： Toll-like receptor adaptive immunity Th1 Th2 regulatory T cell

Potassium and calcium channels in different nerve cells act as therapeutic targets in neurological disorders

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Neural Regeneration Research 2025年第5期20卷 1258-1276页

作者： Qing Qiu Mengting Yang Danfeng Gong Haiying Liang Tingting Chen Department of Pharmacology School of PharmacyNantong UniversityNantongJiangsu ProvinceChina Jiangsu Province Key Laboratory of inflammation and Molecular Drug Target NantongJiangsu ProvinceChina Department of Pharmacy Longyan First Affiliated Hospital of Fujian Medical UniversityLongyanFujian ProvinceChina

The central nervous system, information integration center of the body, is mainly composed of neurons and glial cells. The neuron is one of the most basic and important structural and functional units of the central nervous system, with sensory stimulation and excitation conduction functions. Astrocytes and microglia belong to the glial cell family, which is the main source of cytokines and represents the main defense system of the central nervous system. Nerve cells undergo neurotransmission or gliotransmission, which regulates neuronal activity via the ion channels, receptors, or transporters expressed on nerve cell membranes. Ion channels, composed of large transmembrane proteins, play crucial roles in maintaining nerve cell homeostasis. These channels are also important for control of the membrane potential and in the secretion of neurotransmitters. A variety of cellular functions and life activities, including functional regulation of the central nervous system, the generation and conduction of nerve excitation, the occurrence of receptor potential, heart pulsation, smooth muscle peristalsis, skeletal muscle contraction, and hormone secretion, are closely related to ion channels associated with passive transmembrane transport. Two types of ion channels in the central nervous system, potassium channels and calcium channels, are closely related to various neurological disorders, including Alzheimer's disease, Parkinson's disease, and epilepsy. Accordingly, various drugs that can affect these ion channels have been explored deeply to provide new directions for the treatment of these neurological disorders. In this review, we focus on the functions of potassium and calcium ion channels in different nerve cells and their involvement in neurological disorders such as Parkinson's disease, Alzheimer's disease, depression, epilepsy, autism, and rare disorders. We also describe several clinical drugs that target potassium or calcium channels in nerve cells and could be u

关键词： astrocytes calcium channels central nervous system extracellular ion concentration microglia neurological disorders neurons potassium channels

Multiple checkpoints keep follicular helper T cells under control to prevent autoimmunity

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Cellular & Molecular immunology 2010年第3期7卷 198-203页

作者： Di Yu Carola G Vinuesa Department of immunology and inflammation Garvan Institute of Medical ResearchSydneyNSWAustralia Department of immunology and Genetics John Curtin School of Medical ResearchCanberraACTAustralia

Follicular helper T(Tfh)cells select mutated B cells in germinal centres,which can then differentiate into long-lived high affinity memory B cells and plasma *** cells are regulated by a unique molecular programme orchestrated by the transcriptional repressor *** transcription factor turns down expression of multiple genes,including transcriptional regulators of other T helper lineages and a vast amount of *** enables Tfh cells to express a suite of chemokine receptors,stimulatory ligands and cytokines that enable migration into B-cell follicles,and provision of effective help to B *** surprisingly,dysregulation of this powerful helper subset can lead to a range of autoantibody-mediated diseases;indeed,aberrant accumulation of Tfh cells has been linked with systemic lupus erythematosus,Sjogren’s disease and autoimmune *** we dissect multiple checkpoints that operate throughout Tfh cell development and maturation to maintain immunological tolerance while mounting robust and long-lasting antibody responses.

关键词： autoimmunity germinal centre Tfh

DNA methylation profiles in cancer:functions,therapy,and beyond

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Cancer Biology & Medicine 2024年第2期21卷 111-116页

作者： Jinrong Zhu Yongjie Yang Li Li Jiuren Tang Rongxin Zhang Laboratory of immunology and inflammation School of Life Sciences and BiopharmaceuticsGuangdong Pharmaceutical UniversityGuangzhou 510006China

DNA methylation in cancer DNA methylation,a reversible post-replication modification,defines gene expression and function in different physiologic *** is quite common among global DNA modifications,while promoter hypermethylation often occurs in local regions during cancer,as in CpG island formation,thereby perpetuating the inactivation of tumor suppressor genes.

关键词： cancer suppressor thereby

Reactivation of latent tuberculosis with TNF inhibitors: critical role of the beta 2 chain of the IL-12 receptor

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Cellular & Molecular immunology 2021年第7期18卷 1644-1651页

作者： Marie Robert Pierre Miossec Department of Clinical immunology and Rheumatology and immunogenomics and inflammation research unitUniversity of LyonHôpital Edouard HerriotLyonFrance

Tumor necrosis factor(TNF)inhibitors have improved a lot the treatment of numerous diseases,with the well-known example of rheumatoid arthritis(RA).In the early 2000s,postmarketing data quickly revealed an alarming number of severe tuberculosis(TB)under such *** findings were consistent with previous results in mice where TNF is essential for lymph node formation and granuloma *** effects of TNF inhibition on RA synovium structure are very similar to those on granuloma,with changes in cellular interactions,cytokine,and chemokine *** addition to the role of TNF in granuloma,the interleukin(IL)-12/interferon(IFN)-γpathway is required for an efficient host defense against *** and secondary immunodeficiencies affecting this pathway lead to severe bacillus Calmette-Guérin(BCG)reaction or full *** chronic inflammation as in RA induces a systemic Th1 defect that predisposes to TB through specific downregulation of the IL-12Rß2 *** TNF inhibitors are initiated,this transiently increases this risk of TB,through effects on cellular interactions in a latent TB *** a later stage,when a better control disease activity is obtained,the risk of TB is reduced but not *** the clear benefit from TNF inhibition,latent TB infection screening at baseline is essential for an optimal safety.

关键词： tuberculosis TNF inhibition rheumatoid arthritis cytokines

Reversing the mitochondrial stress-induced exhaustion of CD8^(+)T cells for improving cancer immunotherapy

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Cellular & Molecular immunology 2021年第7期18卷 1634-1637页

作者： Cheng Qian Xuetao Cao National Key Laboratory of Medical immunology Institute of ImmunologySecond Military Medical UniversityShanghaiChina Laboratory of Immunity and inflammation College of Life SciencesNankai UniversityTianjinChina

Antigen-specific CD8+T cells that infiltrate tumor tissue have been considered the primary cytotoxic lymphocytes that exert antitumor effects,building a foundation for current immunotherapies against ***,in the face of continuous antigenic stimulation during chronic infections and cancer,T-cell differentiation leads to a state of incapacitation called T-cell exhaustion,which is a critical barrier to successful T-cell immunotherapy of *** explosive growth of malignant tumor cells accompanied by a dysfunctional vascular system and metabolite competition leads to a stressful tumor microenvironment characterized by low-oxygen tension,acidic interstitial pH,and insufficient *** evidence for the contribution of the tumor microenvironment to the metabolic reprogramming of exhausted CD8+T cells has been increasing,but the response of intratumoral T cells to metabolic stress signals is still not fully *** of a study by Scharping et al.,1 together with other recent evidence,have highlighted that the tumor microenvironment can influence the mitochondrial stress of T cells and drive the trajectory of T-cell differentiation toward *** findings add new perspectives on and insights into the molecular initiators of T-cell exhaustion and the combination of strategies that should be utilized to improve the efficacy of immunotherapy,and these perspectives are discussed in this review.

关键词： immunotherapy cancer stimulation

A role of IL-25,a sibling of IL-17,in triggering psoriatic skin inflammation

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Science China(Life Sciences) 2018年第11期61卷 1437-1438页

作者： Xuemei Tong Bin Li Department of Biochemistry and Molecular Cell Biology Shanghai Key Laboratory for Tumor Microenvironment and InflammationKey Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of EducationShanghai Jiao Tong University School of MedicineShanghai 200025China Shanghai Institute of immunology Shanghai Jiao Tong University School of MedicineChinaDepartment of Immunology and MicrobiologyShanghai Jiao Tong University School of MedicineShanghai 200025China

Interleukin 25(IL-25)expressed in epithelial cells,basophils,eosinophils,mast cells and tuft cells is a member of the IL-17 cytokine *** and colleagues newly found that IL-25 expressed in keratinocytes under pathologi... 详细信息

关键词： IL-17 skin mast

Targeting the P2X7 receptor in microglial cells to prevent brain inflammation

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Neural Regeneration Research 2020年第7期15卷 1245-1246页

作者： Lin-Hua Jiang Sébastien Roger School of Biomedical Sciences Faculty of Biological SciencesUniversity of LeedsSino-UK Joint Laboratory of Brain Function and Injury and Department of Physiology and NeurobiologyXinxiang Medical UniversityXinxiangHenan ProvinceChina EA4245 TransplantationImmunology and InflammationFaculty of MedicineUniversity of ToursToursFrance

Microglial cells are the key innate immune cells in the brain and they are crucial in maintaining brain parenchyma *** physiological conditions,microglial cells assume a ramified morphology with a small cell body and an extensive network of fine processes,which secrete neurotrophic factors and patrol the surroundings in search for pathogens and eliminate cellular debris via *** cells express a repertoire of pattern recognition receptors(PRRs)that enable them to detect diverse danger-associated molecular patterns(DAMPs)released from damaged cells or cells under stress,or pathogen-associated molecular patterns generated by pathogens during infection.

关键词： IL ATP APP Targeting the P2X7 receptor in microglial cells to prevent brain inflammation