STAT4 activation by leukemia inhibitory factor confers a therapeutic effect on intestinal inflammation
文献类型：期刊论文
| 作者 | Zhang, Yanan S.5,7,8; Yue, Jichen5,8; Chin, Y. Eugene5,7,8; Xin, Dazhuan E.7; Wang, Zhizhang7; Sun, Yanyun7; Zou, Quanli C.7; Zhang, Chenxi7; Zhang, Junxun M.7; Zhang, Xiaoren7 |
| 刊名 | EMBO JOURNAL
 |
| 出版日期 | 2019 |
| 卷号 | 38期号:6页码:e99595 |
| ISSN号 | 0261-4189 |
| 关键词 | intestinal inflammation intestinal repair LIF STAT4 Th17-cell differentiation |
| DOI | 10.15252/embj.201899595 |
| 文献子类 | Article |
| 英文摘要 | T helper 17 (Th17)-cell differentiation triggered by interleukin-6 (IL-6) via STAT3 activation promotes inflammation in inflammatory bowel disease (IBD) patients. However, leukemia inhibitory factor (LIF), an IL-6 family cytokine, restricts inflammation by blocking Th17-cell differentiation via an unknown mechanism. Here, we report that microbiota dysregulation promotes LIF secretion by intestinal epithelial cells (IECs) in a mouse colitis model. LIF greatly activates STAT4 phosphorylation on multiple SPXX elements within the C-terminal transcription regulation domain. STAT4 and STAT3 act reciprocally on both canonical cis-inducible elements (SIEs) and noncanonical "AGG" elements at different loci. In lamina propria lymphocytes (LPLs), STAT4 activation by LIF blocks STAT3-dependent Il17a/Il17f promoter activation, whereas in IECs, LIF bypasses the extraordinarily low level of STAT4 to induce YAP gene expression via STAT3 activation. In addition, we found that the administration of LIF is sufficient to restore microbiome homeostasis. Thus, LIF effectively inhibits Th17 accumulation and promotes repair of damaged intestinal epithelium in inflamed colon, serves as a potential therapy for IBD. |
| 学科主题 | Biochemistry & Molecular Biology ; Cell Biology |
| WOS关键词 | INNATE LYMPHOID-CELLS ; ULCERATIVE-COLITIS ; SIGNAL TRANSDUCER ; DENDRITIC CELLS ; LIF RECEPTOR ; TH17 CELLS ; T-CELLS ; TRANSCRIPTION ; EXPRESSION ; CYTOKINE |
| 语种 | 英语 |
| 出版者 | WILEY |
| WOS记录号 | WOS:000461828600001 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/487]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Salk Inst Biol Studies, Immunobiol & Microbial Pathogenesis Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA; 2.Boston Univ, Med Sch, Roger Williams Med Ctr, Dept Surg, Providence, RI USA; 3.Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA; 4.Shanghai Jiao Tong Univ, Sch Med, Shanghai Inst Immunol, Dept Immunol & Microbiol, Shanghai, Peoples R China, 5.Soochow Univ, Med Coll, Inst Biol, Suzhou, Jiangsu, Peoples R China; 6.Harvard Med Sch, Dept Microbiol & Immunobiol, Div Immunol, Boston, MA 02115 USA; 7.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Shanghai, Peoples R China; 8.Soochow Univ, Med Coll, Inst Med Sci, Suzhou, Jiangsu, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Zhang, Yanan S.,Yue, Jichen,Chin, Y. Eugene,et al. STAT4 activation by leukemia inhibitory factor confers a therapeutic effect on intestinal inflammation[J]. EMBO JOURNAL,2019,38(6):e99595. |
| APA | Zhang, Yanan S..,Yue, Jichen.,Chin, Y. Eugene.,Xin, Dazhuan E..,Wang, Zhizhang.,...&Su, Bing.(2019).STAT4 activation by leukemia inhibitory factor confers a therapeutic effect on intestinal inflammation.EMBO JOURNAL,38(6),e99595. |
| MLA | Zhang, Yanan S.,et al."STAT4 activation by leukemia inhibitory factor confers a therapeutic effect on intestinal inflammation".EMBO JOURNAL 38.6(2019):e99595. |
入库方式： OAI收割
来源：上海营养与健康研究所
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