GSTDTAP  > 地球科学
DOI10.1038/s41586-020-2003-8
IL-15, gluten and HLA-DQ8 drive tissue destruction in coeliac disease
Wang, Haibo1; Dienemann, Christian1; Stuetzer, Alexandra2; Urlaub, Henning2,3; Cheung, Alan C. M.4,5; Cramer, Patrick1
2020-01-22
发表期刊NATURE
ISSN0028-0836
EISSN1476-4687
出版年2020
卷号578期号:7796页码:600-+
文章类型Article
语种英语
国家Canada; USA
英文关键词

An HLA- and gluten-dependent mouse model of coeliac disease with villous atrophy provides evidence for the cooperative role of IL-15 and gluten-specific CD4(+) T cells in licensing the full activation of cytotoxic T cells that are necessary for inducing epithelial damage.


Coeliac disease is a complex, polygenic inflammatory enteropathy caused by exposure to dietary gluten that occurs in a subset of genetically susceptible individuals who express either the HLA-DQ8 or HLA-DQ2 haplotypes(1,2). The need to develop non-dietary treatments is now widely recognized(3), but no pathophysiologically relevant gluten- and HLA-dependent preclinical model exists. Furthermore, although studies in humans have led to major advances in our understanding of the pathogenesis of coeliac disease(4), the respective roles of disease-predisposing HLA molecules, and of adaptive and innate immunity in the development of tissue damage, have not been directly demonstrated. Here we describe a mouse model that reproduces the overexpression of interleukin-15 (IL-15) in the gut epithelium and lamina propria that is characteristic of active coeliac disease, expresses the predisposing HLA-DQ8 molecule, and develops villous atrophy after ingestion of gluten. Overexpression of IL-15 in both the epithelium and the lamina propria is required for the development of villous atrophy, which demonstrates the location-dependent central role of IL-15 in the pathogenesis of coeliac disease. In addition, CD4(+) T cells and HLA-DQ8 have a crucial role in the licensing of cytotoxic T cells to mediate intestinal epithelial cell lysis. We also demonstrate a role for the cytokine interferon-gamma (IFN gamma) and the enzyme transglutaminase 2 (TG2) in tissue destruction. By reflecting the complex interaction between gluten, genetics and IL-15-driven tissue inflammation, this mouse model provides the opportunity to both increase our understanding of coeliac disease, and develop new therapeutic strategies.


领域地球科学 ; 气候变化 ; 资源环境
收录类别SCI-E
WOS记录号WOS:000513111200007
WOS关键词T-CELLS ; KILLER-CELLS ; TRANSGLUTAMINASE ; INTERLEUKIN-15 ; EXPRESSION ; DISCOVERY ; RESPONSES ; MODEL ; GENE
WOS类目Multidisciplinary Sciences
WOS研究方向Science & Technology - Other Topics
引用统计
文献类型期刊论文
条目标识符http://119.78.100.173/C666/handle/2XK7JSWQ/281497
专题地球科学
资源环境科学
气候变化
作者单位1.Max Planck Inst Biophys Chem, Dept Mol Biol, Gottingen, Germany;
2.Max Planck Inst Biophys Chem, Bioanalyt Mass Spectrometry, Gottingen, Germany;
3.Univ Med Ctr Gottingen, Inst Clin Chem, Bioanalyt Grp, Gottingen, Germany;
4.UCL, Inst Struct & Mol Biol, Dept Struct & Mol Biol, London, England;
5.Birkbeck Coll, Inst Struct & Mol Biol, Biol Sci, London, England
推荐引用方式
GB/T 7714
Wang, Haibo,Dienemann, Christian,Stuetzer, Alexandra,et al. IL-15, gluten and HLA-DQ8 drive tissue destruction in coeliac disease[J]. NATURE,2020,578(7796):600-+.
APA Wang, Haibo,Dienemann, Christian,Stuetzer, Alexandra,Urlaub, Henning,Cheung, Alan C. M.,&Cramer, Patrick.(2020).IL-15, gluten and HLA-DQ8 drive tissue destruction in coeliac disease.NATURE,578(7796),600-+.
MLA Wang, Haibo,et al."IL-15, gluten and HLA-DQ8 drive tissue destruction in coeliac disease".NATURE 578.7796(2020):600-+.
条目包含的文件
条目无相关文件。
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Wang, Haibo]的文章
[Dienemann, Christian]的文章
[Stuetzer, Alexandra]的文章
百度学术
百度学术中相似的文章
[Wang, Haibo]的文章
[Dienemann, Christian]的文章
[Stuetzer, Alexandra]的文章
必应学术
必应学术中相似的文章
[Wang, Haibo]的文章
[Dienemann, Christian]的文章
[Stuetzer, Alexandra]的文章
相关权益政策
暂无数据
收藏/分享
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。