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    Apoptotic Cell-Directed Resolution of Lung Inflammation Requires Myeloid αv Integrin-Mediated Induction of Regulatory T Lymphocytes.

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    Author
    Zhang, A; Lacy-Hulbert, A; Anderton, S; Haslett, C; Savill, J
    Date
    2020-06
    Source Title
    American Journal of Pathology
    Publisher
    Elsevier BV
    University of Melbourne Author/s
    Savill, John
    Affiliation
    Medicine Dentistry & Health Sciences
    Metadata
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    Document Type
    Journal Article
    Citations
    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.. Am J Pathol, 190 (6), pp.1224-1235. https://doi.org/10.1016/j.ajpath.2020.02.010.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/252368
    DOI
    10.1016/j.ajpath.2020.02.010
    Open Access at PMC
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7254048
    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. 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.

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