Projects per year
Abstract
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 (LPS). 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 labelled apoptotic cells were observed in the majority of CD11c+CD103+ myeloid dendritic cells (DCs) 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 so as to reduce phagocytosis of dying cells by CD103+DCs, exogenous apoptotic cells failed to induce TGF-β1 expression or Treg accumulation and also failed to enhance resolution of LPS-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.
Original language | English |
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Journal | The American Journal of Pathology |
Early online date | 19 Mar 2020 |
DOIs | |
Publication status | E-pub ahead of print - 19 Mar 2020 |
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Dive into the research topics of 'Apoptotic cell-directed resolution of lung inflammation requires myeloid αv integrin-mediated induction of regulatory T lymphocytes'. Together they form a unique fingerprint.Projects
- 1 Finished
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Endogenous suppression of lung inflammation
Savill, J. (Principal Investigator)
1/04/09 → 31/03/16
Project: Research
Equipment
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Institute for Regeneration and Repair Flow Cytometry Facility
Johnston, S. (Manager), Rossi, F. (Manager), Cryer, C. (Other) & Laird, A. (Other)
Institute of Regeneration and RepairFacility/equipment: Facility