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the frequency and skewed t-cell receptor beta-chain variable patterns of peripheral CD4＋CD25＋ regulatory t-cells are associated with hepatitis B e antigen seroconversion of chronic hepatitis B patients during antiviral treatment

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Cellular & Molecular Immunology 2016年第5期13卷 678-687页

作者： Jiezuan Yang Guoping Sheng Dangsheng Xiao Haiyan Shi Wei Wu Haifeng Lu Ping Yi Hongcui Cao Lanjuan Li State Key Laboratory for Diagnosis and treatment of Infectious Diseases Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases The First Affiliated Hospital College of Medicine Zhejiang University Hangzhou 310003 Zhejiang Province PR China

the frequency and t-cell receptor beta-chain variable （tCRBV） patterns of peripheral CD4＋CD25＋ regulatory t-cells （tregs） are ambiguously altered in chronic hepatitis B （CHB） patients following tenofovir disoproxil fumarate （tDF） treatment. Moreover, the clinical significance of these parameters in relation to hepatitis B e antigen （HBeAg） seroconversion （SC） is largely unknown. In this study, the circulation of tregs in HBeAg-positive CHB patients was determined by flow cytometry, and the molecular profiles of frequent tCRBV patterns of tregs were analyzed using a gene melting spectral pattern. the parameters, such as treg frequency, the number of skewed tCRBV patterns, hepatitis B virus （HBV） DNA levels, and alanine aminotransferase （ALt） levels, were analyzed by comparing their associations in seroconverting and non-seroconverting patients following tDF treatment. the treg frequency was significantly correlated with the ALt level in seroconverting but not in non-seroconverting patients. Similarly, skewed tCRBV patterns were remarkably associated with HBV DNA levels in the SC group. Six tCRBV families （BV3, BV11, BV12, BV14, BV20, and BV24） were more prevalent than other tCRBV members in seroconverting patients pretreated with tDF, while BV12, BV15, and BV22 were predominant in non-seroconverting patients during tDF treatment. taken together, the preferential tCRBV patterns may be associated with immune responses related to SC. the dynamic frequency and skewed tCRBV patterns of peripheral tregs could contribute to predicting SC in CHB patients. Moreover, the conserved tCRBV complementarity-determining region （CDR3） motif may be targeted to develop personalized immunotherapy for CHB patients.

关键词： chronic hepatitis B individual treatment gene melting spectral pattern regulatory t-cells t-cell receptorbeta-chain variable

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Interaction between Kynurenine and Aryl Hydrocarbon Receptor in Regulating the Balance of t helper 17 cells and regulatory t-cells in Decidua during Early Gestation

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Reproductive and Developmental Medicine 2018年第1期2卷 8-14页

作者： tian-tian Niu Shao-Liang Yang Ming-Qing Li Hai-Yan Wang Department of Gynecology of Integrated traditional Chinese and Western Medicine Hospital of Obstetrics and GynecologyFudan UniversityShanghai 200090China Laboratory for Reproductive Immunology Hospital of Obstetrics and GynecologyFudan UniversityShanghai 200011China Key Laboratory of Reproduction Regulation of NPFPC SIPPRIRDFudan UniversityShanghai 200032China Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Shanghai 200011China

Objective:to investigate whether kynurenine/aryl hydrocarbon receptor(AHR)affects the maternal-fetal tolerance by involving the differentiation of t helper 17(th17)/regulatory t(treg)cells,and to provide theoretical basic for new treatment of unexplained ***:Flow cytometry(FCM)was used to detect the expression of AHR in peripheral/decidual CD4+t,treg,and th17 *** effect of Kyn on the differentiation of peripheral/decidual naïve t-cells under treg-/th17-polarizing condition was detected by FCM;enzyme-linked immunosorbent assay was performed to examine the level of Kyn in villus and decidual tissues from normal pregnancy(NP)and unexplained abortion(UA).Student’s t-test in the case of two groups or one-way ANOVA in multiple groups was ***:AHR expression in CD4+t-cells was decreased in decidua versus blood in early pregnancy(Pte the differentiation of peripheral and decidual naïve t-cells to th17 cells under treg-polarizing conditions(Pthere was no statistical significance about the concentration of Kyn in decidual or villi tissues between NP and UA,and compared with NP,the expression of AHR in decidual CD4+t-cells from UA was increased(Ptes th17 and restricts treg cells’differentiation,which is involved in maintaining the balance of treg/th17 cells at the maternal-fetal interface.

关键词： Abortion Aryl Hydrocarbon Receptor Kynurenine Maternal-Fetal tolerance regulatory t-cells t helper 17 cells

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regulatory t-cells promote hepatitis B virus infection and hepatocellular carcinoma progression

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Chronic Diseases and translational Medicine 2016年第2期2卷 -页

作者： Wei Li Jun Han Hong Wu Department of Liver Surgery&Liver transplantation Centre West China Hospital Sichuan University Chengdu Sichuan 610041 China Department of Critical Care Medicine Sichuan Provincial Hospital for Women and Children Chengdu Sichuan 610045 China

regulatory t-cells (tregs), known for their immune suppressive function, have been reported in higher numbers, with activated phenotypes and greater potency, in hepatitis B virus (HBV)-related liver diseases than in normal conditions. the numbers, phe-notypes, and function of intrahepatic and/or tumor-infiltrating tregs in HBV-related liver diseases also differ from those of tregs in the peripheral blood. By inhibiting the function of effector t-cells (teffs), tregs play a substantial role in the formation and maintenance of the liver's suppressive microenvironment, which might account for the progression of HBV-related hepatitis and hepatocellular carcinoma (HCC). In acute hepatitis B virus infection, tregs can safeguard the liver from damage at the cost of prolonged antiviral processes, which results in chronic HBV infection in the liver. Furthermore, tregs play a role in the development of cirrhosis, the transformation of cirrhosis to HCC, and the progression and metastasis of HCC. Higher levels of tregs in the peripheral blood and/or tumor sites signify a poorer prognosis in HBV-related liver conditions, and observational data from mouse models and human patients support the theory that depleting tregs may be therapeutic in HBV-related liver diseases by inducing antiviral and antitumor immunity.

关键词： regulatory t-cells Hepatitis B virus Hepatocellular carcinoma

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Clinical significance of programmed cell death-ligand expression in small bowel adenocarcinoma is determined by the tumor microenvironment

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World Journal of Gastroenterology 2023年第40期29卷 5566-5581页

作者： Aitoshi Hoshimoto Atsushi tatsuguchi Ryohei Hamakubo takayoshi Nishimoto Jun Omori Naohiko Akimoto Shu tanaka Shunji Fujimori tsutomu Hatori Akira Shimizu Katsuhiko Iwakiri Department of Gastroenterology Nippon Medical SchoolTokyo 113-8603Japan Department of Analytic Human Pathology Nippon Medical SchoolTokyo 113-8603Japan Department of Pathology Nippon Medical SchoolChiba Hokusoh HospitalChiba 270-1694Japan

BACKGROUND Comprehensive genomic analysis has shown that small bowel adenocarcinoma(SBA)has different genomic profiles from gastric and colorectal ***,it is essential to establish chemotherapeutic regimens based on SBA *** expression of programmed cell death-ligand 1(PD-L1)and programmed cell death-ligand 2(PD-L2)in SBA is not fully ***-PD-L1/PD-1 therapy uses tumor-infiltrating lymphocytes(tILs);therefore,the status of tILs in the tumor microenvironment(tME)may influence their *** ratio of FoxP3+to CD8+t cells has been reported to be useful in predicting the prognosis of digestive system *** to investigate the clinicopathological significance of PD-L1/2 expression according to the status of tILs in SBA *** We performed immunohistochemical analysis for PD-L1,PD-L2,CD8,FoxP3,and DNA mismatch repair(MMR)proteins using formalin-fixed,paraffin-embedded tissues from 50 patients diagnosed with primary *** immunoreactivities of PD-L1 and PD-L2 were determined separately in tumor cells and tumor-infiltrating immune cells throughout the tumor center and invasive margins,and finally evaluated using the combined positive score(CPS).We assessed CD8+and FoxP3+t cells in the intratumoral and tumor-surrounding ***,we calculated and summed the ratio of FoxP3 to CD8+t cell ***-related cell densities were graded as low or *** results were compared with clinicopathological factors and patient *** distribution of cancer-specific survival(CSS)was estimated using the Kaplan–Meier method,and the log-rank test was used to test for significant differences in CSS.A Cox proportional hazard model was also used to assess the effect of tumor variables on *** PD-L1 expression was positive in 34%in tumor cells(t-PD-L1)and 54%in tumor-infiltrating immune cells(I-PDL1)of the cases examined.t-PD-L2 was positive in 34%and I-PD-L2 was positive in 42%of the ***-L1

关键词： Small bowel adenocarcinoma Programmed cell death-ligand 1 Programmed cell death-ligand 2 tumor microenvironment tumor-infiltrating lymphocytes regulatory t-cells

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Effects and possible mechanisms of dexmedetomidine on post-operative cognitive dysfunction

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中华医学杂志（英文版） 2023年第19期136卷 2392-2394页

作者： Huijuan He Manhua Zhu Yupeng Lyu Yuan Yuan Yong Qi China 315000 China 315000

to the Editor: Post-operative cognitive dysfunction (POCD) is described as a series of changes in the neurocognitive conditions and behaviors of patients, which occur within several weeks or even months after anesthesia and surgery. POCD occurs in 20% to 50% of patients, resulting in burden on patients, and exerting a significant social and economic impact. Although an increased understanding of the effects of neuroinflammation and oxidative stress after surgery and anesthesia have clarified the underlying pathophysiology of POCD, many questions remain to be answered. At present, the treatment of POCD mainly focuses on prevention strategies, early identification, and perioperative risk factor management; and an effective treatment is still lacking. Dexmedetomidine (Dex) is a novel and highly selective α2 adrenergic receptor agonist. Perioperative Dex treatment can significantly reduce the incidence of POCD and inflammation, and it can improve postoperative neurocognitive function. Dex may inhibit the massive release of high mobility group protein B1 (HMGB1) by acting on the α2 adrenergic receptor to activate the PI3K/Akt signaling pathway, thus reducing the binding of HMGB1 with toll-like receptor 4 and other membrane proteins, thus playing an anti-inflammatory role. Dex can also enhance HMGB1-induced cognitive decline in inflammatory mice via vagal nerve stimulation. HMGB1 is released extracellularly after cell activation, stress, injury, or death and can promote an inflammatory response. High HMGB1 expression is associated with the occurrence of POCD. the inflammatory immune response may play an important role in the pathogenesis of POCD. regulatory t (treg) cells are key regulatory cells involved in inflammation and play an important role in immune tolerance and ***1can downregulate the immune function of treg cells by decreasing the expression of marker molecules on their surface and inhibiting cytokine secretion. Extracellular HMGB1 also intensifie

关键词： regulatory t-cells ACUtE LUNG INJURY

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Intestinal microbiota: a potential target for the treatment of postmenopausal osteoporosis

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Bone Research 2017年第3期5卷 177-194页

作者： Xin Xu Xiaoyue Jia Longyi Mo Chengcheng Liu Liwei Zheng Quan Yuan Xuedong Zhou State Key Laboratory of Oral Diseases West China Hospital of Stomatology Sichuan University Department of Cariology and Endodontics West China Hospital of Stomatology Sichuan University Department of Periodontics West China Hospital of Stomatology Sichuan University Department of Pediatric Dentistry West China Hospital of Stomatology Sichuan University Department of Dental Implantology West China Hospital of Stomatology Sichuan University

Postmenopausal osteoporosis （PMO） is a prevalent metabolic bone disease characterized by bone loss and structural destruction, which increases the risk of fracture in postmenopausal women. Owing to the high morbidity and serious complications of PMO, many efforts have been devoted to its prophylaxis and treatment. the intestinal microbiota is the complex community of microorganisms colonizing the gastrointestinal tract. Probiotics, which are dietary or medical supplements consisting of beneficial intestinal bacteria, work in concert with endogenous intestinal microorganisms to maintain host health. Recent studies have revealed that bone loss in PMO is closely related to host immunity, which is influenced by the intestinal microbiota. the curative effects of probiotics on metabolic bone diseases have also been demonstrated. the effects of the intestinal microbiota on bone metabolism suggest a promising target for PMO management. this review seeks to summarize the critical effects of the intestinal microbiota and probiotics on PMO, with a focus on the molecular mechanisms underlying the pathogenic relationship between bacteria and host, and to define the possible treatment options.

关键词： CHAIN FAttY-ACIDS BONE-MINERAL DENSItY tUMOR-NECROSIS-FACtOR INCREASE CALCIUM-ABSORPtION EStROGEN-RECEPtOR-ALPHA regulatory t-cells LONG-tERM CONSUMPtION GUt MICROBIOtA VItAMIN-D PARACELLULAR PERMEABILItY

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Dynamic changes in the systemic immune responses of spinal cord injury model mice

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Neural Regeneration Research 2021年第2期16卷 382-387页

作者： tian-Yun Gao Fei-Fei Huang Yuan-Yuan Xie Wen-Qing Wang Liu-Di Wang Dan Mu Yi Cui Bin Wang Clinical Stem Cell Center the Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjingJiangsu ProvinceChina Department of Radiology the Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjingJiangsu ProvinceChina Reproductive and Genetic Center of National Research Institute for Family Planning BeijingChina

Intraspinal inflammatory and immune responses are considered to play central roles in the pathological development of spinal cord *** study aimed to decipher the dynamics of systemic immune responses,initiated by spinal cord *** spinal cord in mice was completely transected at *** in the in vivo inflammatory response,between the acute and subacute stages,were observed.A rapid decrease in C-reactive protein levels,circulating leukocytes and lymphocytes,spleen-derived CD4~+interferon-γ+t-helper cells,and inflammatory cytokines,and a marked increase in neutrophils,monocytes,and CD4~+CD25~+FOXP3~+regulatory t-cells were observed during the acute *** systemic immune alterations were gradually restored to basal levels during the sub-acute *** the acute phase of spinal cord injury,systemic immune cells and factors showed significant inhibition;however,this inhibition was transient,and the indicators of these serious disorders gradually returned to baseline levels during the subacute *** experiments were performed in accordance with the institutional animal care guidelines,approved by the Institutional Animal Care and Use Committee of Experimental Animal Center of Drum tower Hospital,China(approval No.2019 AE01040)on June 25,2019.

关键词： C-reactive protein immune dysfunction inflammation inflammatory cytokines regulatory t-cells spinal cord injury systemic immune response t-helper cells

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