Apoptotic Cell–Directed Resolution of Lung Inflammation Requires Myeloid αv Integrin–Mediated Induction of Regulatory T Lymphocytes
| Autor: | John Savill, Adam Lacy-Hulbert, Stephen M. Anderton, Ailiang Zhang, Christopher Haslett |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Adoptive cell transfer Myeloid Phagocytosis CD11c Apoptosis chemical and pharmacologic phenomena C-C chemokine receptor type 7 Inflammation Lymphocyte Activation T-Lymphocytes Regulatory Article Lymphocyte Depletion Pathology and Forensic Medicine Mice 03 medical and health sciences 0302 clinical medicine medicine Animals ITGB8 Experimental Lung Inflammation Chemistry Forkhead Transcription Factors hemic and immune systems Pneumonia Integrin alphaV Adoptive Transfer 030104 developmental biology medicine.anatomical_structure Cancer research medicine.symptom 030215 immunology |
| Zdroj: | The American Journal of Pathology Zhang, A, Lacy-Hulbert, A, Anderton, S, Haslett, C & Savill, J 2020, ' Apoptotic cell-directed resolution of lung inflammation requires myeloid αv integrin-mediated induction of regulatory T lymphocytes ', American Journal of Pathology . https://doi.org/10.1016/j.ajpath.2020.02.010 |
| ISSN: | 0002-9440 |
| DOI: | 10.1016/j.ajpath.2020.02.010 |
| Popis: | Intratracheal instillation of apoptotic cells enhances resolution of experimental lung inflammation by incompletely understood mechanisms. We report that this intervention induces functional regulatory T lymphocytes (Tregs) in mouse lung experimentally inflamed by intratracheal administration of lipopolysaccharide. Selective depletion demonstrated that Tregs were necessary for maximal apoptotic cell–directed enhancement of resolution, and adoptive transfer of additional Tregs was sufficient to promote resolution without administering apoptotic cells. After intratracheal instillation, labeled apoptotic cells were observed in most CD11c+CD103+ myeloid dendritic cells migrating to mediastinal draining lymph nodes and bearing migratory and immunoregulatory markers, including increased CCR7 and β8 integrin (ITGB8) expression. In mice deleted for αv integrin in the myeloid line to reduce phagocytosis of dying cells by CD103+ dendritic cells, exogenous apoptotic cells failed to induce transforming growth factor-β1 expression or Treg accumulation and failed to enhance resolution of lipopolysaccharide-induced lung inflammation. We conclude that in murine lung, myeloid phagocytes encountering apoptotic cells can deploy αv integrin–mediated mechanisms to induce Tregs and enhance resolution of acute inflammation. |
| Databáze: | OpenAIRE |
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