Tissue environment, not ontogeny, defines murine intestinal intraepithelial T lymphocytes
| Autor: | Harriet Watt, Mahima Swamy, Dina Dikovskaya, Olivia J. James, Alejandro Brenes, Laura Spinelli, Angus I. Lamond, Jens L. Hukelmann, Maud Vandereyken |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Proteomics Mouse Proteome immunometabolism Cell Lymphocyte Activation intestinal immunity Immunology and Inflammation 0302 clinical medicine Tandem Mass Spectrometry Homeostasis Biology (General) Intestinal Mucosa Receptor Intraepithelial Lymphocytes Chromatography High Pressure Liquid 0303 health sciences General Neuroscience hemic and immune systems General Medicine Cell biology Phenotype medicine.anatomical_structure Cellular Microenvironment Medicine medicine.symptom tissues Research Article Signal Transduction Spectrometry Mass Electrospray Ionization QH301-705.5 Science T lymphocytes chemical and pharmacologic phenomena Inflammation Biology digestive system General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Downregulation and upregulation medicine Animals Cell Lineage Transcription factor 030304 developmental biology General Immunology and Microbiology fungi Mice Inbred C57BL Biomarkers 030217 neurology & neurosurgery CD8 |
| Zdroj: | eLife eLife, Vol 10 (2021) |
| ISSN: | 2050-084X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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