BLT1 in dendritic cells promotes Th1/Th17 differentiation and its deficiency ameliorates TNBS-induced colitis
文献类型：期刊论文
| 作者 | Zhou, Jinfeng2; Lai, Weiming2; Yang, Wanjie2; Pan, Juping1; Shen, Hu1; Cai, Yingying2; Yang, Cuixia2; Ma, Ningjia2; Zhang, Yue2; Zhang, Ru2 |
| 刊名 | CELLULAR & MOLECULAR IMMUNOLOGY
 |
| 出版日期 | 2018-12 |
| 卷号 | 15期号:12页码:1047-1056 |
| ISSN号 | 1672-7681 |
| DOI | 10.1038/s41423-018-0030-2 |
| 文献子类 | Article |
| 英文摘要 | Leukotriene B4 (LTB4) synthesis is enhanced in the colonic mucosa in patients with inflammatory bowel disease (IBD). BLT1, a high-affinity receptor for LTB4, exhibits no effect on the progression of dextran sodium sulfate (DSS)-induced colitis, which mostly relies on innate immunity. Here, we reported that BLT1 regulates trinitrobenzene sulfonic add (TNBS)-induced colitis, which reflects CD4(+) T-cell-dependent adaptive immune mechanisms of IBD. We found that BLT1 signaling enhanced the progression of colitis through controlling the production of proinflammatory cytokines by dendritic cells (DCs) and modulating the differentiation of Th1 and Th17. BLT1(-/-) mice displayed an alleviated severity of TNBS-induced colitis with reduced body weight loss and infiltrating cells in the lamina propria. BLT1 deficiency in DCs led to reduced production of proinflammatory cytokines, including IL-6, TNF-alpha, and IL-12, and these results were further confirmed via treatment with a BLT1 antagonist. The impaired cytokine production by BLT1(-/-) DCs subsequently led to reduced Th1 and Th17 differentiation both in vitro and in vivo. We further performed a conditional DC reconstitution experiment to assess whether BLT1 in DCs plays a major role in regulating the pathogenesis of TNBS-induced colitis, and the results indicate that BLT1 deficiency in DCs also significantly reduces disease severity. The mechanistic study demonstrated that BLT1-regulated proinflammatory cytokine production through the Gai beta gamma subunit-phospholipase C beta (PLC beta)-PKC pathway. Notably, we found that treatment with the BLT1 antagonist also reduced the production of proinflammatory cytokines by human peripheral blood DCs. Our findings reveal the critical role of BLT1 in regulating adaptive immunity and TNBS-induced colitis, which further supports BLT1 as a potential drug target for adaptive immunity-mediated IBD. |
| WOS关键词 | LEUKOTRIENE B-4 RECEPTOR ; INTESTINAL INFLAMMATION ; MOUSE MODEL ; TH17 CELLS ; ACTIVATION ; EXPRESSION ; PATHOGENESIS ; REQUIREMENT ; ANTAGONIST ; MECHANISMS |
| 资助项目 | Ministry of Science and Technology of China[2014CB541903] ; National Natural Science Foundation of China[31171348] ; National Natural Science Foundation of China[31371414] ; Fundamental Research Funds for the Central Universities[00000000] |
| WOS研究方向 | Immunology |
| 语种 | 英语 |
| 出版者 | CHIN SOCIETY IMMUNOLOGY |
| WOS记录号 | WOS:000451835100005 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279479]  |
| 专题 | 国家新药筛选中心 |
| 通讯作者 | Gao, Yuan; Du, Changsheng |
| 作者单位 | 1.Tongji Univ, Tongji Hosp, Tongji Univ branch, Shanghai 200092, Peoples R China; 2.Tongji Univ, Sch Life Sci & Technol, Shanghai Key Lab Signaling & Dis Res, Putuo Dist Peoples Hosp, Shanghai 200092, Peoples R China; 3.Tsinghua Univ, Inst Immunol, Beijing 100086, Peoples R China; 4.Tsinghua Univ, Sch Med, Beijing 100086, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Zhou, Jinfeng,Lai, Weiming,Yang, Wanjie,et al. BLT1 in dendritic cells promotes Th1/Th17 differentiation and its deficiency ameliorates TNBS-induced colitis[J]. CELLULAR & MOLECULAR IMMUNOLOGY,2018,15(12):1047-1056. |
| APA | Zhou, Jinfeng.,Lai, Weiming.,Yang, Wanjie.,Pan, Juping.,Shen, Hu.,...&Du, Changsheng.(2018).BLT1 in dendritic cells promotes Th1/Th17 differentiation and its deficiency ameliorates TNBS-induced colitis.CELLULAR & MOLECULAR IMMUNOLOGY,15(12),1047-1056. |
| MLA | Zhou, Jinfeng,et al."BLT1 in dendritic cells promotes Th1/Th17 differentiation and its deficiency ameliorates TNBS-induced colitis".CELLULAR & MOLECULAR IMMUNOLOGY 15.12(2018):1047-1056. |
入库方式： OAI收割
来源：上海药物研究所
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