期刊
ELIFE
卷 10, 期 -, 页码 -出版社
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.70055
关键词
T lymphocytes; intestinal immunity; proteomics; immunometabolism; Mouse
类别
资金
- Wellcome Trust [105024/Z/14/Z, 206246/Z/17/Z, 073980/Z/03/Z, 098503/E/12/Z, 215309/Z/19/Z, 222320/Z/21/Z]
- Wellcome Trust [222320/Z/21/Z, 098503/E/12/Z, 206246/Z/17/Z] Funding Source: Wellcome Trust
Studies have shown that induced T-IEL and natural T-IEL subsets exhibit differences in their proteomes and metabolic pathways, indicating a significant impact of the gut environment on T-IEL phenotypes. Features such as the skewing of the cell surface repertoire, energy barrier, and high cholesterol levels in T-IEL help maintain their homeostasis and function.
Tissue-resident intestinal intraepithelial T lymphocytes (T-IEL) patrol the gut and have important roles in regulating intestinal homeostasis. T-IEL include both induced T-IEL, derived from systemic antigen-experienced lymphocytes, and natural T-IEL, which are developmentally targeted to the intestine. While the processes driving T-IEL development have been elucidated, the precise roles of the different subsets and the processes driving activation and regulation of these cells remain unclear. To gain functional insights into these enigmatic cells, we used high-resolution, quantitative mass spectrometry to compare the proteomes of induced T-IEL and natural T-IEL subsets, with naive CD8(+) T cells from lymph nodes. This data exposes the dominant effect of the gut environment over ontogeny on T-IEL phenotypes. Analyses of protein copy numbers of >7000 proteins in T-IEL reveal skewing of the cell surface repertoire towards epithelial interactions and checkpoint receptors; strong suppression of the metabolic machinery indicating a high energy barrier to functional activation; upregulated cholesterol and lipid metabolic pathways, leading to high cholesterol levels in T-IEL; suppression of T cell antigen receptor signalling and expression of the transcription factor TOX, reminiscent of chronically activated T cells. These novel findings illustrate how T-IEL integrate multiple tissue-specific signals to maintain their homeostasis and potentially function.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据