دورية أكاديمية
أعرض في EDS

Tissue environment, not ontogeny, defines murine intestinal intraepithelial T lymphocytes.

التفاصيل البيبلوغرافية
العنوان: Tissue environment, not ontogeny, defines murine intestinal intraepithelial T lymphocytes.
المؤلفون: Brenes AJ; Centre for Gene Regulation and Expression, University of Dundee, Dundee, United Kingdom.; Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee, United Kingdom., Vandereyken M; MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, United Kingdom., James OJ; MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, United Kingdom., Watt H; MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, United Kingdom., Hukelmann J; Centre for Gene Regulation and Expression, University of Dundee, Dundee, United Kingdom., Spinelli L; Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee, United Kingdom., Dikovskaya D; MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, United Kingdom., Lamond AI; Centre for Gene Regulation and Expression, University of Dundee, Dundee, United Kingdom., Swamy M; Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee, United Kingdom.; MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, United Kingdom.
المصدر: ELife [Elife] 2021 Sep 02; Vol. 10. Date of Electronic Publication: 2021 Sep 02.
نوع المنشور: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012-
مواضيع طبية MeSH: Cell Lineage* , Cellular Microenvironment* , Lymphocyte Activation* , Proteome* , Proteomics*, Intestinal Mucosa/*metabolism , Intraepithelial Lymphocytes/*metabolism, Animals ; Biomarkers/metabolism ; Chromatography, High Pressure Liquid ; Homeostasis ; Intestinal Mucosa/immunology ; Intraepithelial Lymphocytes/immunology ; Male ; Mice, Inbred C57BL ; Phenotype ; Signal Transduction ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry ; Mice
مستخلص: 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.
Competing Interests: AB, OJ, HW, JH, LS, DD, AL, MS None, MV none
(© 2021, Brenes et al.)
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معلومات مُعتمدة: 222320/Z/21/Z United Kingdom WT_ Wellcome Trust; 098503/E/12/Z United Kingdom WT_ Wellcome Trust; 206246/Z/17/Z United Kingdom WT_ Wellcome Trust; 073980/Z/03/Z United Kingdom WT_ Wellcome Trust; United Kingdom WT_ Wellcome Trust; 105024/Z/14/Z United Kingdom WT_ Wellcome Trust; 215309/Z/19/Z United Kingdom WT_ Wellcome Trust
فهرسة مساهمة: Keywords: T lymphocytes; immunology; immunometabolism; inflammation; intestinal immunity; mouse; proteomics
المشرفين على المادة: 0 (Biomarkers)
0 (Proteome)
تواريخ الأحداث: Date Created: 20210902 Date Completed: 20211018 Latest Revision: 20240226
رمز التحديث: 20240226
مُعرف محوري في PubMed: PMC8463072
DOI: 10.7554/eLife.70055
PMID: 34473623
قاعدة البيانات: MEDLINE
الوصف
تدمد:2050-084X
DOI:10.7554/eLife.70055