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Neural Regeneration Research 2025年第10期20卷 2895-2897页

作者： Nicolas Hugues Yu Luo Department of Molecular and Cellular Biosciences University of CincinnatiCincinnatiOHUSA Neuroscience Graduate program University of CincinnatiCincinnatiOHUSA Division of immunobiology Cincinnati Children’s Hospital Medical CenterUniversity of Cincinnati College of MedicineCincinnatiOHUSA

Adult microglia,by continuously sensing changes in their environment and communicating with nearly all brain cell types,are considered to be the immune sentinels of the *** the healthy central nervous system(CNS),microglia display a unique molecular homeostatic signature(i.e.,Tmem119,P2ry12,Sall1,Siglech,Gpr34,and Hexb)(Figure 1A).

关键词： Figure signature critical

Perspectives on the role of mTORC2 in B lymphocyte development,immunity and tumorigenesis

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Protein & Cell 2011年第7期2卷 523-530页

作者： Adam S.Lazorchak Bing Su Department of immunobiology and the Vascular Biology and Therapeutic program Yale School of MedicineNew HavenCT 06519USA

Mammalian target of rapamycin complex 2(mTORC2)is a key downstream mediator of phosphoinositol-3-kinase(PI3K)dependent growth factor *** lymphocytes,mTORC2 has emerged as an important regulator of cell development,homeostasis and immune ***,our current understanding of mTORC2 functions and the molecular mechanisms regulating mTORC2 signaling in B and T cells are still largely *** studies have begun to shed light on this important *** have previously reported that mTORC2 mediates growth factor dependent phosphorylation of Akt and facilitates Akt dependent phosphorylation and inactivation of transcription factors FoxO1 and *** have recently explored the functions of mTORC2 in B cells and show that mTORC2 plays a key role in regulating survival and immunoglobulin(Ig)gene recombination of bone marrow B cells through an Akt2-FoxO1 dependent *** recombination is suppressed in proliferating B cells to ensure that DNA double strand breaks are not generated in actively dividing *** results raise the possibility that genetic or pharmacologic inhibition of mTORC2 may promote B cell tumor development as a result of inefficient suppression of Ig recombination in dividing B *** also propose a novel strategy to treat cancers based on our recent discovery that mTORC2 regulates Akt protein stability.

关键词： mTOR lymphocyte B cell cancer mTORC2 FoxO Akt Sin1

Id1 has a physiological role in regulating early B lymphopoiesis

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Cellular & Molecular Immunology 2011年第1期8卷 41-49页

作者： Shawn W Cochrane Ying Zhao S Scott Perry Thomas Urbaniak Xiao-Hong Sun immunobiology and Cancer Research program Oklahoma Medical Research FoundationOklahoma CityOKUSA Department of Cell Biology University of Oklahoma Health Sciences CenterOklahoma CityOKUSA

Basic helix–loop–helix E proteins play critical roles in B-cell development by stimulating B cell-specific gene expression and immunoglobulin gene *** function of E proteins can be effectively suppressed by their naturally occurring inhibitors,Id1 to *** expression of Id1 has been shown to block B-cell development at the early pro-B cell ***,whether Id1 plays a physiological role in controlling B lymphopoiesis was not *** Id1-deficient mice do not exhibit significant abnormalities in steady-state B lymphopoiesis,we detected more robust B-cell engraftment in transplant recipients of Id1-deficient bone marrow compared to those of wild-type donor *** culture,Id1 ablation dramatically enhances B-lineage cell production without any marked effects on myeloid ***,Id1 expression was found in pro-B but not pre-B cells as measured by enhanced green fluorescent protein(EGFP)fluorescence and by quantitative reverse *** loss of Id1 did not alter the number of B-cell colonies generated from whole bone marrow or the proliferation rate of developing B cells,B-cell colonies were detectable at a much earlier time point and the size of the colonies were ***,we infer that Id1-deficient progenitors possess higher potential to differentiate to the pre-B cell stage when a proliferative burst *** together,we present evidence to suggest that Id1 plays a physiological role in restraining the developmental progression,which may be important for proper B-cell differentiation in the bone marrow.

关键词： Id1 helix-loop-helix E2A B cell differentiation

Endocrine impact of Helicobacter pylori:Focus on ghrelin and ghrelin o-acyltransferase

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World Journal of Gastroenterology 2011年第10期17卷 1249-1260页

作者： Penny L Jeffery Michael A McGuckin Sara K Linden Mucosal Diseases program Mater Medical Research InstituteMater Health Services Mucosal immunobiology and Vaccine Center Sahlgrenska AcademyUniversity of Gothenburg

Ghrelin is predominantly produced by the gastric enteroendocrine cell compartment and is octanoylated by the recently discovered ghrelin o-acyltransferase （GOAT） before secretion into the bloodstream. This octanoylation is essential for many of the biological properties of ghrelin including appetite stimulation and anti-inflammatory properties as only the acylated form of ghrelin binds to the ghrelin receptor, the growth hormone secretagogue receptor （GHS-R）. Given the gastric location of ghrelin production, it is perhaps not surprising that insult to the gastric mucosa affects circulating ghrelin levels in humans. Helicobacter pylori （H. pylon） infects more than fifty percent of the world＇s population and once established within the gastric mucosa, can persist for life. Infection is associated with chronic gastritis, gastric atrophy and ulceration, reduced appetite and a lower body mass index （BMI）. The large majority of studies investigating levels of circulating ghrelin and ghrelin expression in the stomach in patients with H. pylori infection indicate that the bacterium has a negative impact on ghrelin production and/or secretion. Eradication of infection restores ghrelin, improves appetite and increases BMI in some studies, however, a causative relationship between H. pylori-associated serum ghrelin decline and food intake and obesity has not been established. Most studies measure total ghrelin in the circulation although the measurement of the ratio of acyl/total ghrelin gives a clearer indication that the ghrelin acylation process is altered during infection and atrophy. GOAT is essential for the production of biologically-active, acyl ghrelin and the impact of H. pylori on GOAT expression and activity will be highly informative in the future.

关键词： Appetite Ghrelin Ghrelin o-acyltransferase Helicobacterpylori Infection Inflammation Obesity

Metabolic regulation of T cell development by Sinl-mTORC2 is mediated by pyruvate kinase M2

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Journal of Molecular Cell Biology 2019年第2期11卷 93-106页

作者： Xinxing Ouyang Yuheng Han Guojun Qu Man Li Ningbo Wu Hongzhi Liu Omotooke Arojo Hongxiang Sun Xiaobo Liu Dou Liu Lei Chen Qiang Zou Bing Su Shanghai Institute of Immunology Department of Immunology and Microbiology Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education Shanghai Jiao Tong University School of Medicine Shanghai 200025 China Department of immunobiology and the Vascular Biology and Therapeutics program Yale University School of Medicine 333 Cedar Street New Haven CT 06520 USA

Glucose metabolism plays a key role in thymocyte development. The mammalian target of rapamycin complex 2 (mT0RC2) is a critical regulator of cell growth and metabolism, but its role in early thymocyte development and metabolism has not been fully studied. We show here that genetic ablation of Sinl, an essential component of mTORC2, in T lineage cells results in severely impaired thymocyte development at the CD4^- CD8^- double negative (DN) stages but not at the CD4^+ CD8^+ double positive (DP) or later stages. Notably, Sinl-deficient DN thymocytes show markedly reduced proliferation and ***, we discover that the M2 isoform of pyruvate kinase (PKM2) is a novel and crucial Sinl effector in promoting DN thymocyte development and metabolism. At the molecular level, we show that Sinl-mTORC2 controls PKM2 expression through an AKT-dependent PPAR-y nuclear translocation. Together, our study unravels a novel mTORC2-PPAR-γ-PKM2 pathway in immune-metabolic regulation of early thymocyte development.

关键词： mT0RC2 Sinl thymocyte development PPAR-γ PKM2 metabolism

D-半乳糖葡胺增敏小鼠对非致死剂量细菌脂多糖致死作用与肝脏DNA片段化的高度相关性(英文)

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Acta Pharmacologica Sinica 2003年第3期24卷 3-8页

作者：周炳荣 ,Marina GUMENSCHEIMER,Marina FREUDENBERG,Chris GALANOS Max-Planck-Institute for immunobiology Stiibeweg 51 D-79108 Freiburg i Br Germany Max-Planck-Institute for immunobiology Stiibeweg 51 D-79108 Freiburg i Br Germany Max-Planck-Institute for immunobiology Stiibeweg 51 D-79108 Freiburg i Br Germany

目的:本实验研究了以非致死剂量脂多糖(Lipopolysaccharide,LPS)攻击半乳糖葡胺(D-galactosamine,D-GalN)增敏小鼠的死亡是否伴有重要器官的凋亡特征。方法:实验组小鼠以LPS(0.05μg)与D-GalN(20mg)直接攻击,而对照组小鼠仅仅以LPS或D-G... 详细信息

目的:本实验研究了以非致死剂量脂多糖(Lipopolysaccharide,LPS)攻击半乳糖葡胺(D-galactosamine,D-GalN)增敏小鼠的死亡是否伴有重要器官的凋亡特征。方法:实验组小鼠以LPS(0.05μg)与D-GalN(20mg)直接攻击,而对照组小鼠仅仅以LPS或D-GalN,在规定实验时间经乙醚麻醉后,取出脑、肾、心、脾、肺、肝,并立即匀浆和抽提DNA,对所抽提的各器官的DNA以常规琼脂糖凝胶电泳分析是否存在DNA梯度现象;并测定血浆中乳酸脱氢酶和谷氨酸草酰乙酸转移酶,同时将DNA片段化现象与小鼠致死作用的关联性在实验组和对照组间做比较。结果:LPS攻击B-GalN增敏的小鼠4h时,在所检测的器官中,仅仅肝脏可见到凋亡特征DNA片段化现象,至7h时小鼠死亡。而仅用LPS或D-GalN攻击的对照组小鼠,不仅全部存活而且肝脏DNA分子完整。结论:LPS攻击B-GalN增敏的小鼠,肝脏是唯一出现DNA片段化的靶器官,由细菌LPS引发小鼠的死亡,肝脏的损伤可能是关键的原因。

关键词：脂多糖类 D-半乳糖葡胺细胞凋亡 DNA断片

Phenotypic Tfh development promoted by CXCR5-controlled re-localization and IL-6 from radiation-resistant cells

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Protein & Cell 2015年第11期6卷 825-832页

作者： Xin Chen Weiwei Ma Tingxin Zhang LongyanWu Hai Qi Tsinghua-Peking Center for Life Sciences Tsinghua University Beijing 100084 China Laboratory of Dynamic immunobiology Institute for Immunology School of Medicine Tsinghua University Beijing 100084 China

How follicular T-helper （Tfh） cells develop is incom- pletely understood. We find that, upon antigen exposure in vivo, both naive and antigen-experienced T cells sequentially upregulate CXCR5 and Bc16 within the first 24 h, relocate to the T-B border, and give rise to phenotypic Bcl6＋CXCR5＋ Tfh cells before the first cell division. CXCR5 upregulation is more dependent on ICOS costimulation than that of Bcl6, and early Bcl6 induction requires T-cell expression of CXCR5 and, presumably, relocation toward the follicle. This early and rapid upregulation of CXCR5 and Bcl6 depends on IL-6 produced by radiation-resistant cells. These results suggest that a Bcl6hiCXCR5hi phenotype does not automatically define a Tfh lineage but might reflect a state of antigen exposure and non-commitment to terminal effector fates and that niches in the T-B border and/or the follicle are important for optimal Bcl6 induction and maintenance.

关键词： Tfh CXCR5 Bcl6 radiation-resistant cell,IL-6

Microenvironmental influences on T cell immunity in cancer and inflammation

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Cellular & Molecular Immunology 2022年第3期19卷 316-326页

作者： Darren R.Heintzman Emilie L.Fisher Jeffrey C.Rathmell Department of Pathology Microbiologyand ImmunologyVanderbilt University Medical CenterNashvilleTN37205USA Vanderbilt Center for immunobiology Vanderbilt University Medical CenterNashvilleTN37205USA

T cell metabolism is dynamic and highly *** the intrinsic metabolic programs of T cell subsets are integral to their distinct differentiation and functional patterns,the ability of cells to acquire nutrients and cope with hostile microenvironments can limit these pathways.T cells must function in a wide variety of tissue settings,and how T cells interpret these signals to maintain an appropriate metabolic program for their demands or if metabolic mechanisms of immune suppression restrain immunity is an area of growing *** in inflamed and cancer tissues,a wide range of changes in physical conditions and nutrient availability are now acknowledged to shape *** include fever and increased temperatures,depletion of critical micro and macro-nutrients,and accumulation of inhibitory waste *** we review several of these factors and how the tissue microenvironment both shapes and constrains immunity.

关键词： immunometabolism T cell microenvironment cancer inflammation

Anti-TOSO antibody treatment promotes T cell activation-induced cell death(AICD) in vitro and in vivo

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Chinese Science Bulletin 2014年第13期59卷 1374-1385页

作者： Yi Tan Xue Han Xiaoran Wu Qiao Xing Lieping Chen Shengdian Wang Key Laboratory of Infection and Immunity Institute of Biophysics Chinese Academy of Sciences University of Chinese Academy of Sciences Department of immunobiology Yale University School of Medicine

T cell activation-induced cell death(AICD),that involves the induction of Fas-mediated apoptosis,is very important for the maintenance of immune *** was firstly described as an inhibitor of Fasmediated apoptosis and overexpressed in chronic lymphocytic ***,TOSO was identified as IgM *** this study,we produced anti-TOSO monoclonal antibody(mAb)that could block the binding of IgM to TOSO and found that T cell apoptosis is negatively correlated with TOSO expression during T cell *** of activated T cells with anti-TOSO blocking mAb promoted T cell AICD in in vitro AICD model,and treatment of xenogeneic-GVHD mice with the antibody also increased the sensitivity of activated T cells to Fasinduced apoptosis,which was accompanied by reduction of c-FLIPL expression and up-regulation of AP-1 *** summary,our data indicate the anti-apoptotic effect of TOSO in T cell AICD and open up new therapeutic prospects for the treatment of hematologic malignancies and immune disorders.

关键词： T细胞活化单克隆抗体细胞死亡治疗诱导体外 Fas介导淋巴细胞白血病

Faecal microbiota transplantation in patients with Clostridium difficile and significant comorbidities as well as in patients with new indications:A case series

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World Journal of Gastroenterology 2017年第39期23卷 7174-7184页

作者： Perttu Lahtinen Eero Mattila Veli-Jukka Anttila Jyrki Tillonen Matti Teittinen Pasi Nevalainen Seppo Salminen Reetta Satokari Perttu Arkkila Department of Gastroenterology Paijat-Hame Central HospitalLahti 15850Finland Department of Infectious Diseases Helsinki University Hospital Department of Medicine Hyvinkaa Hospital Department of Medicine Tampere University Hospital Functional Foods Forum University of Turku immunobiology Research program Faculty of MedicineUniversity of Helsinki Department of Gastroenterology Helsinki University Hospital

Fecal microbiota transplantation(FMT) is effective in recurrent Clostridium difficile infection(r CDI). Knowledge of the safety and efficacy of FMT treatment in immune deficient patients is scarce. FMT has been suggested as a potential method for an increasing number of new indications besides r CDI. Among our FMT-treated r CDI patients, we reviewed those with major comorbidities: two human immunodeficiency virus patients, six haemodialysis patients, two kidney transplant patients, two liver transplant patients and a patient with chronic lymphatic leukaemia. We also reviewed those treated with FMT for indications other than r CDI: Salmonella carriage(two patients), trimethylaminuria(two patients), small intestinal bacterial overgrowth(SIBO;one patient), and lymphocytic colitis(one patient), as well as a common variable immunodeficiency patient with chronic norovirus infection and ESBL-producing Escherichia coli(E. coli) carriage. Of the thirteen r CDI patients treated with FMT, eleven cleared the CDI. The observed adverse events were not directly attributable to FMT. Concerning the special indications, both Salmonellas and ESBL-producing E. coli were eradicated. One trimethylaminuria patient and one SIBO-patient reported a reduction of symptoms. Three patients did not experience a benefit from FMT: chronic norovirus, lymphocytic colitis and the other fish malodour syndrome. There were no reported side effects in this group. FMT appeared to be safe and effective for immunocompromised patients with r CDI. FMT showed promise for the eradication of antibiotic-resistant bacteria, but further research is warranted.

关键词： Faecal microbiota transplantation Antibiotic resistance Clostridium difficile infection Microbiota Immunodeficiency Salmonella infection