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the kinase p38αfunctions in dendritic cells to regulate th2-cell differentiation and allergic inflammation

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Cellular & Molecular Immunology 2022年第7期19卷 805-819页

作者： Miaomiao Han Jingyu Ma Suidong Ouyang Yanyan Wang Tingting Zheng Peishan Lu Zihan Zheng Weiheng Zhao Hongjin Li Yun Wu Baohua Zhang Ran Hu Kinya Otsu Xinguang Liu Ying Wan Huabin Li Gonghua Huang ENT Institute and Department of Otorhinolaryngology Eye&ENT HospitalFudan University200031 ShanghaiChina Shanghai Institute of Immunology Shanghai Jiao Tong University School of Medicine200025 ShanghaiChina Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics Guangdong Medical University523808 DongguanChina Biomedical Analysis Center Army Medical University400038 ChongqingChina Department of Cardiovascular Medicine Graduate School of MedicineOsaka UniversityOsaka 565-0871Japan School of Cardiovascular Medicine and Sciences King’s College LondonLondon SE59NUUK Present address:Tongji Hospital Tongji Medical CollegeHuazhong University of Science and Technology430030 WuhanChina Department of Dermatology Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese Medicine200437 ShanghaiChina Department of Clinical Laboratory Medicine Shanghai Tenth People’s Hospital of Tongji University200072 ShanghaiChina Present address:Basic Department of Cancer Center Shanghai Tenth People’s Hospital of Tongji University200072 ShanghaiChina

Dendritic cells(DCs)play a critical role in controlling T helper 2(th2)cell-dependent diseases,but the signaling mechanism that triggers this function is not fully *** showed that p38αactivity in DCs was decreased upon HDM stimulation and dynamically regulated by both extrinsic signals and th2-instructive cytokines.p38α-specific deletion in cDC1s but not in cDC2s or macrophages promoted th2 responses under HDM *** study showed that p38αin cDC1s regulated th2-cell differentiation by modulating the MK2−c-FOS−IL-12 ***,crosstalk between p38α-dependent DCs and th2 cells occurred during the sensitization phase,not the effector phase,and was conserved between mice and *** results identify p38αsignaling as a central pathway in DCs that integrates allergic and parasitic instructive signals with th2-instructive cytokines from the microenvironment to regulate th2-cell differentiation and function,and this finding may offer a novel strategy for the treatment of allergic diseases and parasitic infection.

关键词： Allergy p38α dendritic cell th2

A critical regulation of th2 cell responses by RORa in allergic asthma

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Science China(Life Sciences) 2021年第8期64卷 1326-1335页

作者： Jeong-Eun Lee Garam Cho Minkyoung Cho Daehong Kim Mi-Ock Lee Yeonseok Chung Laboratory of Immune Regulation Research Institute of Pharmaceutical SciencesCollege of PharmacySeoul National UniversitySeoul 08826Republic of Korea BK21 Plus Program College of PharmacySeoul National UniversitySeoul 08826Republic of Korea

Allergic asthma is a chronic inflammatory disease of the lung and the airway,which is characterized by aberrant type 2 immune responses to otherwise unharmful *** the central role of th2 cells and type 2 cytokines in the pathogenesis of allergic asthma is well documented,the regulation and plasticity of th2 cells remain incompletely *** using an animal model of allergic asthma in IL-4-reporter mice,we found that th2 cells in the lung expressed higher levels of Rora than those in the lymph nodes,and that treatment with an RORa agonist SRI 078 resulted in diminished th2 cell responses in *** determine the T cell-intrinsic role of RORa in allergic asthma in vivo,we established T cell-specific RORa-deficient^(f/f)fyf(Cd4creRora^(f/f))*** intranasal allergen challenges,Cd4creRora^(f/f)mice exhibited a significantly increased th2 cells in the lungs and the airway and showed an enhanced eosinophilic inflammation compared to littermate control *** with Foxp3^(YFP-cre)Rora^(f/f)mice and CD^(8+)T cell depletion showed that the increased th2 cell responses in the Cd4creRora^(f/f)mice were independent of Treg cells and CD^(8+)T *** findings demonstrate a critical regulatory role of RORa in th2 cells,which suggest that RORa agonists could be effective for the treatment of allergic diseases.

关键词： th2 allergic critical

Effect of PPARγagonist(rosiglitazone)on the secretion of th2 cytokine in asthma mice

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Asian Pacific Journal of Tropical Medicine 2017年第1期10卷 63-66页

作者： Ji-Hui Yu Li Long Zhi-Xiao Luo Jie-Ru You Department of Physical Examination the First Affiliated Hospital of Chongqing Medical UniversityChongqing400016China

Objective: To explore the effect of PPAR γ agonist(rosiglitazone) on the secretion of th2 cytokines and the proportion of immune cell subsets in asthma mice,Methods: Ovalbumin(OVA)-sensitized mice were used to build asthma models,those mice were divided into the normal control group,model group and rosiglitazone group,Differences of the changes in lung histopathology of mice in the three group were observed through hematoxylin and eosin(HE) strain,and the numbers of the total cells,eosinophils and neutrophils in BALF of mice in the three groups were compared,ELISA and real-time PCR were employed to detect the protein levels of interleukin(IL)-5,IL-13,IL-4 and IL-10 and m RNA level,respectively,Flow cytometry number was implied to analyze the proportion of immune cell subsets in peripheral blood of mice,Results: Compared with the mice in the control group,and mice of the model group,the infiltration of inflammatory cells in BALF increased,bronchial smooth muscle became thickened,a large amount of collagen deposited,the secretion of th2 cytokine increased significantly,the ratio of regulatory T cells(Treg) decreased,the ratio of T17 cells rose distinctly; while in mice of the rosiglitazone group,the changes of their lung histopathology were improved obviously,the number of infiltration of inflammatory cells declined,the thickened smooth muscle relieved,the deposition of collagen decreased,the secretion of th2 cytokine was inhibited,the ratio of Treg went up,and the increased of the ratio of T17 cells was inhibited but still not return to normal level,Conclusions: Rosiglitazone can regulate the proportion of Treg and th17 cells and inhibit the secretion of th2 cytokines,which inhibit the airway inflammatory response for asthma mice effectively.

关键词： PPAR γ Asthma th2 Treg th17

Caraway extract alleviates atopic dermatitis by regulating oxidative stress,suppressing th2 cells,and upregulating th1 cells in mice

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Asian Pacific Journal of Tropical Biomedicine 2022年第10期12卷 421-429页

作者： Fardin Khajepour Mohammad Reza Zangouyee Arezu Khosravimashizi Ali Afgar Vahideh Abdollahi Shahriar Dabiri Reza Nosratabadi Department of Medical Immunology Afzalipour Faculty of MedicineKerman University of Medical SciencesKermanIran Research Center for Hydatid Disease in Iran Afzalipour Faculty of MedicineKerman University of Medical SciencesKermanIran Student Research Committee Afzalipour Faculty of MedicineKerman University of Medical SciencesKermanIran Department of Animal Biology Kharazmi UniversityTehranIran Department of Pathology Afzalipour Faculty of MedicineKerman University of Medical SciencesKermanIran Pathology and Stem Cells Research Center Afzalipour Faculty of MedicineKerman University of Medical SciencesKermanIran Gastroenterology and Hepathology Research Center Institute of Basic and Clinical Physiology SciencesKerman University of Medical SciencesKermanIran

Objective:To explore the anti-inflammatory and antioxidant effects of caraway on atopic dermatitis(AD)in ***:AD was induced in two stages,including sensitization and challenge with the application of 2,4 dinitrochlorobenzene 2% and 0.2%,*** symptoms and histological analysis of the skin were *** effects of caraway on oxidant/antioxidant parameters as well as th1-and th2-related cytokines were also ***:Caraway reduced the severity of dermatitis in AD-induced mice,as evidenced by significant inhibition of th2-related cytokines(IL-4 and IL-13)and increased th1-related cytokine(IFN-γ).Additionally,treatment with caraway significantly increased superoxide dismutase and catalase activity and decreased the malondialdehyde level in the serum of AD ***,caraway inhibited the differentiation of th2 cells while favoring th1 cell differentiation in the spleen via regulating their master transcription factors GATA3 and ***:Caraway could improve AD autoimmune responses and could be considered a potential candidate to treat AD disease.

关键词： Carum carvi L. Caraway Atopic dermatitis 2,4 dinitrochlorobenzene th2 th1 Oxidative stress

Electroacupuncture Alleviates Neuropathic Pain by Modulating th2 Infiltration and Inhibiting Microglial Activation in the Spinal Cord of Rats with Spared Nerve Injury

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World Journal of Traditional Chinese Medicine 2020年第4期6卷 448-455页

作者： Bin Liu Wei Long Ru-Rong Wang Depar tment of Anesthesiology West China Hospital of Sichuan UniversityChengduChina

Objective:the objective is to explore the potential mechanisms mediating the analgesic effect of electroacupuncture(EA)for neuropathic *** and Methods:Sprague-Dawley(SD)rats were used to establish a spared nerve injury(SNI)model of neuropathic *** intensity of neuropathic pain was measured by assessing the mechanical withdrawal threshold and thermal withdrawal *** analysis and western blotting were performed to evaluate the activation of microglia and Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)signaling in the L4-6 spinal cord of SD *** infiltration of th2 and expression of interleukin-10(IL-10)in the L4-6 spine were analyzed by flow cytometry and enzyme-linked immunosorbent ***:Behavioral test results demonstrated that SNI-induced hyperalgesia was significantly ameliorated by EA stimulation at"Zusanli"(ST36)and"Yanglingquan"(GB34)*** addition,EA therapy significantly suppressed microglia activation and phosphorylation of JAK2/STAT3 in the L4-6 spine of rats with ***,EA promoted the infiltration of th2 and secretion of IL-10 in the L4-6 spine of rats with ***:the study findings indicate that EA stimulation mediated the infiltration of th2 in the spinal cord of rats with *** addition,EA inhibited microglial activation in the L4-6 spine of rats with SNI.

关键词： Electroacupuncture Janus kinase/signal transducer and activator of transcription signaling microglia neuropathic pain th2

Curcumin regulated shift from th1 to th2 in trinitrobenzene sulphonic acid-induced chronic colitis

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Acta Pharmacologica Sinica 2006年第8期27卷 1071-1077页

作者： Ming ZHANG~(3,4) Chang-sheng DENG~1 Jia-ju ZHENG~2 Jian XIA~1 ~1Department of Gastroenterology,Zhongnan Hospital of Wuhan University,Wuhan 430071,China ~2Municipal Hospital of Suzhou,Suzhou 215008,China ~3Department of Gastroenterology,Drum Tower Hospital of Nanjing,Nanjing 210008,China 3Department of Gastroenterology Drum Tower Hospital of Nanjing Nanjing 210008 China 1Department of Gastroenterology Zhongnan Hospital of Wuhan University Wuhan 430071 China 2Municipal Hospital of Suzhou Suzhou 215008 China 1Department of Gastroenterology Zhongnan Hospital of Wuhan University Wuhan 430071 China

Aim:To investigate the therapeutic effects of curcumin（Cur）on trinitrobenzenesulphonic acid（TNBS）-induced colitis and the effects of Cur on the balance ofth1/th2 ***:Colitis was induced by TNBS and treated with Cur(***-1·d-1,ip),dexamethasone(Dex,2 mg·kg-1·d-1),or Cur plus dexamethasone(Cur+Dex,30 ***-1·d-1Cur ip+2 ***-1·d-1Dex,ip).mRNA in colon mucosawere detected by real-time quantitative polymerase chain *** were detected by flow cytometry and concentrations of cytokines insera were detected by enzyme-linked immunosorbent ***:Both Curand Dex improved body weight loss,ameliorated histological images and de-creased macroscopic score and myeloperoxidase *** decreased the ex-pression of th1 cytokines（IL-12,IFN-γ,TNF-α,IL-1）and increased the expres-sion of th2 cytokines（IL-4 and IL-10）in colon *** also increased theproportion of IFN-γ/IL-4 in splenocytes and *** and Cur+Dex de-creased the expression of th1 cytokines but could not increase the expression ofth2 cytokines and the proportion of IFN-γ/***:Cur exerted thera-peutic effects on colitis by regulating the shift from th1 to th2.

关键词： colitis curcumin IL-4 IL-12 th1 th2

th1、th2免疫应答与小儿常见自身免疫病

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复旦学报（医学版） 2002年第3期29卷 197-199页

作者：郭桂梅郭履赒苏贻新王晓川复旦大学附属儿科医院内科

目的　了解常见自身免疫病桥本甲状腺炎 (HT)、幼年型特发性关节炎 (JIA)及系统性红斑狼疮 (SLE)患儿机体th1、th2免疫应答状况 ,探讨th1、th2应答失常与上述疾病的关系。方法　ELISA法检测患儿和对照组PBMC经ConA刺激后上清液中细胞因... 详细信息

目的　了解常见自身免疫病桥本甲状腺炎 (HT)、幼年型特发性关节炎 (JIA)及系统性红斑狼疮 (SLE)患儿机体th1、th2免疫应答状况 ,探讨th1、th2应答失常与上述疾病的关系。方法　ELISA法检测患儿和对照组PBMC经ConA刺激后上清液中细胞因子的水平。结果　多数HT患儿IL 4/IFN γ比值低于对照组 (P th1细胞介导的器官特异性自身免疫病。s JIA患儿th2应答占优势 ,而非器官特异性自身免疫病SLE则th1应答增强 ,但不能仅用th1或th2应答增强全面解释其发病机制。

关键词： T淋巴细胞亚群细胞因子免疫调控自身免疫病小儿免疫应答 th1 th2

CTLA4 Silencing with siRNA Promotes Deviation of th1/th2 in Chronic Hepatitis B Patients

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Cellular & Molecular Immunology 2009年第2期6卷 123-127页

作者： Yongsheng Yu Hao Wu Zhenghao Tang Guoqing Zang Department of Infectious Diseases. Sixth People＇s Hospital Shanghai Jiaotong University Shanghai 200233 China

To determine whether RNA interference （RNAi） could block cytotoxic T-lymphocyte antigen 4 （CTLA4） in human lymphocytes in vitro and promote IFN-T and IL-2 secretions, three small interfering RNAs （siRNAs） were selected based on target specificity sequences of human CTLA4 and transfected into human lymphocytes of chronic HBV patients. As a result, the expression of human CTLA4 mRNA was efficiently suppressed by all the three siRNAs. Compared with negative control （siRNA-co）, siRNA-1 inhibited the expression of CTLA4 most efficiently and was used in the further study. the expressions of IFN-γ and IL-2 were upregulated and the level of IL-4 was almost unchanged in lymphocytes transfected with siRNA-1 compared with the blank control. these results indicated that siRNA-1 led to IFN-γ and IL-2 secretions, which is a main response of th1/th2. In a conclusion, RNAi significantly suppressed the expression of human CTLA4 mRNA in human lymphocytes in vitro, and could induce th1/th2 response. It could be a new therapeutic strategy for chronic HBV infection.

关键词： CTLA4 siRNA lymphocyte th1 th2

Activated rat hepatic stellate cells influence th1/th2 profile in vitro

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World Journal of Gastroenterology 2015年第23期21卷 7165-7171页

作者： Zhi-Zhi Xing Liu-Ye Huang Cheng-Rong Wu Hong You Hong Ma Ji-Dong Jia Department of Gastroenterology Yantai Yuhuangding Hospital Affiliated to Medical College of Qingdao University Liver Research Center Beijing Friendship Hospital Capital Medical University

AIM: To investigate the effects of activated rat hepatic stellate cells(HSCs) on rat th1/th2 profile in ***: Growth and survival of activated HSCs and CD4+ T lymphocytes cultured alone or together was assessed after 24 or 48 h. CD4+ T lymphocytes were then cultured with or without activated HSCs for 24 or 48 h and the proportion of th1 [interferon(IFN)-γ+] and th2 [interleukin(IL)-4+] cells was assessed by flow cytometry. th1 and th2 cell apoptosis was assessed after 24 h of co-culture using a caspase-3 staining procedure. Differentiation rates of th1 and th2 cells from CD4+ T lymphocytes that were positive for CD25 but did not express IFN-γ or IL-4 were also assessed after 48 h of co-culture with activated HSCs. Galectin-9 expression in HSCs was determined by immunofluorescence and Western blotting. ELISA was performed to assess galectin-9 secretion from activated ***: Co-culture of CD4+ T lymphocytes with activated rat HSCs for 48 h significantly reduced the proportion of th1 cells compared to culture-alone conditions(-1.73% ± 0.71%; P the proportion of th2 cells was not altered; the th1/th2 ratio was significantly decreased(-0.44 ± 0.13; P the level of IFN-γ in th1 cells wasdecreased(-65.71 ± 9.67; P the level of IL-4 in th2 cells was increased(82.79 ± 25.12; P th1(12.27% ± 0.99%; P th2(1.71% ± 0.185%; P th activated HSCs; the th1 cell apoptosis rate was significantly higher than in th2 cells(P the differentiation of th1 and th2 cells; however, the increase in the proportion of th2 cells was significantly higher than that of th1 cells(1.85% ± 0.4

关键词： Hepatic stellate cells th1 cells th2 cells Galectin-9