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Type I and II interferons enhance dendritic cell maturation and migration capacity by regulating cd38 and cd74 that have synergistic effects with TLR agonists

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Cellular & Molecular Immunology 2011年第4期8卷 341-347页

作者： Thanh-Nhan Nguyen-Pham Mi-Seon Lim Truc Anh Thi Nguyen Youn-Kyung Lee Chun-Ji Jin Hyun Ju Lee Cheol Yi Hong Jae-Sook Ahn Deok-Hwan Yang Yeo-Kyeoung Kim Ik-Joo Chung Byoung Chul Park Hyeoung-Joon Kim Je-Jung Lee Research Center for Cancer Immunotherapy Chonnam National University Hwasun HospitalJeollanamdoKorea Department of Hematology-Oncology Chonnam National UniversityGwangjuKorea The Brain Korea 21 Project Center for Biomedical Human Resources at Chonnam National UniversityGwangjuKorea Vaxcell-Bio Therapeutics JeollanamdoKorea Korea Research Institute of Bioscience and Biotechnology(KRIBB) DaejeonKorea

The major limitation for the maturation of dendritic cells(DCs)using Toll-like receptor(TLR)agonists is their decreased ability to migrate into lymph nodes compared with conventional ***38 can be used as a multifunctional marker to modulate migration,survival and Th1 responses of ***74 has been shown to negatively regulate DC *** goal of this study was to investigate the combinations of TLR agonists and interferons(IFNs)that most effectively regulate cd38 and cd74 expression on *** TLR agonist stimulation in combination with IFN-a and IFN-c was the best method for regulating cd38 and cd74 expression and inducing the highest secretion of *** in vitro migration assay showed that DCs treated with this combination had significantly enhanced migratory ability,similar to that observed in cells expressing cd38,cd74 and *** results of this study suggest that an alternative maturation protocol in which two TLR ligands are combined with type I and II IFNs generates potent DCs that have both a high migratory capacity and high IL-12p70 production.

关键词： cd38 cd74 dendritic cells interferon Toll-like receptor

Effect of cd74 on the prognosis of patients with resectable pancreatic cancer

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Hepatobiliary & Pancreatic Diseases International 2014年第1期13卷 81-86页

作者： Jun-Feng Zhang Rong Hua De-Jun Liu Wei Liu Yan-Miao Huo Yong-Wei Sun Department of General Surgery Renji Hospital School of Medicine Shanghai Jiaotong University

BACKGROUND: cd74 is known as a type II transmembrane glycoprotein that is associated with the major histocompatibility complex class II α and β chains. Recent studies have demonstrated that the expression of cd74 is also linked to some forms of tumors. The present study was to assess the effect of cd74 expression on the prognosis of resectable pancreatic ductal adenocarcinoma(PDAC). METHODS: Forty-six patients who had received a curative resection of primary PDAC and postoperative chemotherapy were included in this study. Immunohistochemical staining was conducted of cd74 on paraffin-embedded tumor sample slices. The patients were grouped according to cd74 staining: cd74(-): cd74 positive tumor cells cd74(+): cd74 positive tumor cells ≥25%. The correlation of cd74 expression level with clinicopathological features and cumulative survival rate was calculated. RESULTS: The numbers of cd74(+) and(-) patients were 32 and 14, respectively. cd74(+) patients showed a high rate of perineural invasion(P=0.007). The 3- and 5-year cumulative survival rates of cd74(-) patients were significantly higher than those of cd74(+) patients(62% and 41% vs 9% and 0%, P=0.000). Multivariate analysis showed that cd74 expression and lymphatic permeation were the independent prognostic indicators. CONCLUSIONS: The overexpression of cd74 is a key factor associated with perineural invasion. Lower-stage(I and II) PDAC patients with cd74 overexpression have a poor prognosis even if they receive a curative resection. cd74 can be used as a prognostic indicator for resectable PDAC.

关键词： cd74 pancreatic ductal adenocarcinoma perineural invasion cumulative survival rate prognosis

cd74 is a survival receptor on colon epithelial cells

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World Journal of Gastroenterology 2010年第26期16卷 3258-3266页

作者： Nitsan Maharshak Sivan Cohen Frida Lantner Gili Hart Richard Bucala Idit Shachar Department of Immunology Weizmann Institute of Science Rehovot 76100 Israel Department of Gastroenterology and Liver Diseases Tel Aviv Sourasky Medical Center Affiliated to the Sackler Faculty of Medicine Tel Aviv University Tel Aviv 69978 Israel Department of Medicine Yale University School of Medicine New Haven CT 06520 United States

AIM: To investigate the expression and function of cd74 in normal murine colon epithelial cells (CEC) and colon carcinoma cells. METHODS: Expression of cd74 mRNA and protein were measured by reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting and fluorescence-activated cell sorter (FACS). The effect of migration inhibitory factor (MIF) on the survival of normal CEC from C57BL/6, NOD/SCID, and cd74 def icient mice both in vitro and in vivo, and on the CT26 carcinoma cell line was analyzed by (quantitative) qRT-PCR, RTPCR, Western blotting and FACS. RESULTS: cd74 was found to be expressed on normalCEC. Stimulation of cd74 by MIF induced a signaling cascade leading to up-regulation of Bcl-2 expression, resulting in a signif icant increased survival of CEC. cd74 was also expressed on the CT26 colon carcinoma cell line and its stimulation by MIF resulted in enhanced cell survival, up-regulation of Akt phosphorylation and Bcl-2 expression.

关键词： cd74 Migration inhibitory factor Colon epithelial cells

cd74 in antigen presentation,inflammation,and cancers of the gastrointestinal tract

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World Journal of Gastroenterology 2009年第23期15卷 2855-2861页

作者： Ellen J Beswick Victor E Reyes Department of Pediatrics University of Texas Medical Branch Galveston TX 77555 United States Department of Pediatrics and Microbiology and Immunology University of Texas Medical Branch Galveston TX 77555 United States

cd74 is a protein whose initial role in antigen presentation was recognized two decades ago. Recent studies have revealed that it has additional functions as a receptor for macrophage migration inhibitory factor and as a receptor for an important human pathogen, Helicobacter pylori （H pylon）. The role of cd74 as a receptor is important because after binding of migration inhibitory factor or H pylori, NF-κB and Erkl/2 activation occurs, along with the induction of proinflammatory cytokine secretion. This review provides an up-to-date account of the functions of cd74 and how it might be involved in inflammation and cancer within the gastrointestinal tract.

关键词： cd74 Invariant chain Cancer Inflammation Helicobacterpylori Gastrointestinal tract

cd74基因对重症肌无力患者胸腺上皮细胞IFN-γR基因表达的影响

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细胞与分子免疫学杂志 2011年第7期27卷 730-732页

作者：李倩如臧文巧高峰杜英张清勇郑州大学基础医学院微生物学与免疫学教研室河南郑州450001 河南省医学科学研究所河南郑州450052 郑州大学第二附属医院胸外科河南郑州450000

目的:探讨cd74基因对重症肌无力患者胸腺上皮细胞(TEC)IFN-γR基因表达的影响。方法:原代培养重症肌无力患者胸腺上皮细胞,脂质体法转染pCMV-cd74,荧光定量RT-PCR法检测转染结果及TEC中IFN-γR等与自身免疫病相关基因mRNA水平的表达。结... 详细信息

目的:探讨cd74基因对重症肌无力患者胸腺上皮细胞(TEC)IFN-γR基因表达的影响。方法:原代培养重症肌无力患者胸腺上皮细胞,脂质体法转染pCMV-cd74,荧光定量RT-PCR法检测转染结果及TEC中IFN-γR等与自身免疫病相关基因mRNA水平的表达。结果:原代培养并传代的胸腺上皮细胞转染pCMV-cd74质粒后,cd74基因的表达显著提高。TEC高表达cd74基因,可引起HLA-A、ECFG1、IL-4R、IL-32和IFN-γR基因表达显著增加。结论:cd74基因对TEC表达IFNγR基因有明显的促进作用。

关键词： cd74 胸腺上皮细胞 IFN-γR 自身免疫相关基因

利用酵母双杂交系统鉴定MIF与cd74胞外片段间的相互作用

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南方医科大学学报 2009年第12期29卷 2383-2386,2390页

作者：单志新林秋雄邓春玉谭虹虹邝素娟肖定璋朱杰宁符永恒余细勇广东省人民医院医学研究中心/广东省心血管病研究所广东广州510080

目的利用酵母双杂交系统鉴定巨噬细胞移动抑制因子(MIF)与Ⅱ型穿膜蛋白cd74胞外片段间可能的相互作用区域。方法利用分子克隆技术,分别构建以pGBKT7为载体的人全长MIF、MIF50-65、MIF1-50/65-115的重组诱饵质粒,以pGADT7为载体的人cd747... 详细信息

目的利用酵母双杂交系统鉴定巨噬细胞移动抑制因子(MIF)与Ⅱ型穿膜蛋白cd74胞外片段间可能的相互作用区域。方法利用分子克隆技术,分别构建以pGBKT7为载体的人全长MIF、MIF50-65、MIF1-50/65-115的重组诱饵质粒,以pGADT7为载体的人cd7473-232、cd7473-109、cd74109-149、cd74149-232的重组激活域(AD)质粒。用PEG/LiAC法将上述重组诱饵质粒分别与重组AD质粒两两共转化感受态酵母菌AH109,分别观察在SD/-Trp-Leu、含X-α-gal的SD/-Trp-Leu-Ade-His培养基上生长情况。结果限制性内切酶酶切和DNA测序证实所构建的重组质粒全部正确。3种重组诱饵质粒转化的酵母菌AH109均可在SD/-trp上生长,4种重组AD质粒转化的酵母菌AH109均可在SD/-leu上生长,而且上述转化的酵母菌AH109均无自身转录激活活性。只有MIF、MIF50-65、MIF1-50/65-115与cd7473-232表达质粒共转化的酵母菌AH109可在SD/-Trp-Leu-Ade-His培养基上生长,能激活MEL1报告基因,使X-α-gal变蓝。结论MIF能以功能域MIF50-65非依赖性方式与完整的cd74胞外片段相互结合,进行细胞信号转导。

关键词：酵母双杂交巨噬细胞移动抑制因子 cd74 蛋白质相互作用克隆,分子

cd74的抗原递呈和免疫调节及高效免疫载体功能研究进展

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细胞与分子免疫学杂志 2018年第8期34卷 757-760页

作者：陈芳芳刘雪兰余为一安徽农业大学动物科技学院安徽合肥230036

cd74又称主要组织相容性复合体(MHC)Ⅱ相关恒定链(Ii)。它的基本功能是辅助MHCⅡ类分子递呈外源性抗原肽,启动特异性体液免疫应答。近年来发现,cd74还参与MHCⅠ类分子递呈内源性抗原和细胞免疫应答。cd74也是巨噬细胞迁移抑制因子(MIF)... 详细信息

cd74又称主要组织相容性复合体(MHC)Ⅱ相关恒定链(Ii)。它的基本功能是辅助MHCⅡ类分子递呈外源性抗原肽,启动特异性体液免疫应答。近年来发现,cd74还参与MHCⅠ类分子递呈内源性抗原和细胞免疫应答。cd74也是巨噬细胞迁移抑制因子(MIF)的受体,在炎症和抗感染等反应中具有免疫调节功能。正是基于在辅助抗原递呈和免疫调节中的功能,cd74还被用作高效免疫载体,由于表现出双靶向进入Ⅰ类和Ⅱ类分子递呈抗原途径的优点和具有增强体液免疫和细胞免疫效果的作用,得到广泛应用。我们总结了cd74的辅助递呈抗原、免疫调节和高效载体的三种作用。

关键词： cd74 主要组织相容性复合体(MHC) 抗原递呈免疫调节免疫载体综述

Identification of the interactions between the truncated fragments of acrophage migration inhibitory factor and cd74 using yeast two-hybrid system

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Identification of the interactions between the truncated fra...

中国病理生理学会受体和信号转导专业委员会暨消化专业委员会联合学术会议

作者： Zhixin Shan Qiuxiong Lin Chunyu Deng Honghong Tan Sujuan Kuang Dingzhang Xiao Jiening Zhu Yongheng Fu Xiyong Yu Research Center of Medical Sciences,Guangdong General Hospital,Guangzhou 510080,China Guangdong Provincial Cardiovascular Institute,Guangzhou 510080,China.

To investigate the interaction domains between macrophage migration inhibitory factors(MIF) and the extracellular segment of type- II trans-membrane protein cd74 using yeast two-hybrid *** using molecular cloning techniques,the DNA fragments encoding MIF,MIF and MIF were introduced into the pGBKT7 vector to construct the corresponding recombinant bait plasmids,and the DNA fragments encoding cd74,cd74,cd741 and cd74 were introduced into the pGADT7 vector to construct the corresponding recombinant activation domain(AD) plasmids,respectively. By using PEG/ LiAC method,the above 3 recombinant bait plasmids were transformed into the chemical competent yeast AHI09 cells with the 4 recombinant AD plasmids in one-one assembly manner,*** the transformed yeast AH109 cells were screened consecutively on the SD/-Trp-Leu and the SD/-Trp-Leu-Ade-His/X-a-gal nutritional *** results of restrictive endonuclease digestion and DNA sequencing proved that all the recombinant plasmids used in this study were *** yeast AHI09 cells transformed with each of the 3 recombinant bait plasmids could grow on the SD/-trp nutritional media without autonomous activation effect on the reporter gene MEL1,and the yeast AH109 cells transformed with each of the 4 recombinant AD plasmids could also grow on the SD/-leu nutritional media without autonomous activation effect on the reporter gene *** the yeast AHI09 cells co-transformed respectively with MIF,MIF,MIF expression plasmid and cd7473-232 expression plasmid could grow on the SD/-Trp-Leu-Ade-His nutritional media with the activation on the transcription of reporter gene *** interacts with the integrity extracellular segment of cd74(cd74) independent of the function domain of MIF.To investigate the interaction domains between macrophage migration inhibitory factors(MIF) and the extracellular segment of type- II trans-membrane protein cd74 using yeast two-hybrid *** using molecular cloning techniqu

关键词： yeast two-hybrid system macrophage migration inhibitory factor cd74 protein interaction cloning molecular

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胃腺癌中cd74蛋白的表达及其临床意义

临床与实验病理学杂志 2016年第11期32卷 1273-1275页

作者：崔丽娟刘智夏勤李林丰四川省遂宁市中心医院病理科 629000

目的探讨cd74蛋白在胃腺癌组织中的表达及其临床意义,为临床医师判断肿瘤预后及靶向治疗提供新的可行性参考指标。方法选取手术切除胃腺癌患者58例不伴HP感染,同时选取正常胃黏膜20例作为对照。采用免疫组化SP两步法检测胃腺癌组织中cd7... 详细信息

目的探讨cd74蛋白在胃腺癌组织中的表达及其临床意义,为临床医师判断肿瘤预后及靶向治疗提供新的可行性参考指标。方法选取手术切除胃腺癌患者58例不伴HP感染,同时选取正常胃黏膜20例作为对照。采用免疫组化SP两步法检测胃腺癌组织中cd74的表达,分析其与各临床病理特征间的关系。结果胃腺癌中cd74的阳性检出率(74.1%)高于正常组(13.3%),差异有统计学意义。cd74在胃腺癌患者中表达增高与肿瘤分期及淋巴结转移有关,与患者年龄、性别、肿瘤大小、浸润深度、肿瘤分化程度、有/无复发无关。cd74阳性检出率随肿瘤分期增高而上升,伴淋巴结转移的患者cd74阳性检出率较未转移者高(Pcd74阳性者生存时间比cd74阴性者生存时间短(P=0.007)。结论 cd74可作为胃腺癌预后判断的一项独立指标及新的治疗靶点,cd74阳性胃腺癌患者预后较差。

关键词：胃肿瘤腺癌 cd74 免疫组织化学预后