Environmental cues regulate epigenetic reprogramming of airway-resident memory CD8+ T cells
| Autor: | Christopher D. Scharer, Sarah L. Hayward, Jeremy M. Boss, Jacob E. Kohlmeier, Emily K. Cartwright, Shiki Takamura, Zheng-Rong Tiger Li |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Programmed cell death Cellular immunity Cell Survival Immunology Cell Apoptosis Biology CD8-Positive T-Lymphocytes Immunological memory Article Epigenesis Genetic 03 medical and health sciences Mice 0302 clinical medicine Orthomyxoviridae Infections medicine Immunology and Allergy Integrated stress response Cytotoxic T cell Animals Epigenetics Lung respiratory system Cellular Reprogramming Cell biology respiratory tract diseases Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Cellular Microenvironment Mucosal immunology Female Reprogramming Immunologic Memory 030215 immunology |
| Zdroj: | Nature Immunology |
| ISSN: | 1529-2916 1529-2908 |
| Popis: | Tissue-resident memory T cells (TRM cells) are critical for cellular immunity to respiratory pathogens and reside in both the airways and the interstitium. In the present study, we found that the airway environment drove transcriptional and epigenetic changes that specifically regulated the cytolytic functions of airway TRM cells and promoted apoptosis due to amino acid starvation and activation of the integrated stress response. Comparison of airway TRM cells and splenic effector-memory T cells transferred into the airways indicated that the environment was necessary to activate these pathways, but did not induce TRM cell lineage reprogramming. Importantly, activation of the integrated stress response was reversed in airway TRM cells placed in a nutrient-rich environment. Our data defined the genetic programs of distinct lung TRM cell populations and show that local environmental cues altered airway TRM cells to limit cytolytic function and promote cell death, which ultimately leads to fewer TRM cells in the lung. Kohlmeier and colleagues showed that the airway environment drove transcriptional and epigenetic changes that regulated the cytolytic functions of airway TRM cells and promoted their apoptosis due to amino acid starvation and activation of the integrated stress response. |
| Databáze: | OpenAIRE |
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