Non-classical tissue monocytes and two functionally distinct populations of interstitial macrophages populate the mouse lung

Joey Schyns, Qiang Bai, Cecilia Ruscitti, Coraline Radermecker, Sebastiaan Schepper, Svetoslav Chakarov, Frédéric Farnir, Dimitri Pirottin, Florent Ginhoux, Guy Boeckxstaens, Fabrice Bureau and Thomas Marichal ()
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Joey Schyns: Liège University
Qiang Bai: Liège University
Cecilia Ruscitti: Liège University
Coraline Radermecker: Liège University
Sebastiaan Schepper: KU Leuven
Svetoslav Chakarov: A*STAR, Biomedical Grove 8a
Frédéric Farnir: Liège University
Dimitri Pirottin: Liège University
Florent Ginhoux: A*STAR, Biomedical Grove 8a
Guy Boeckxstaens: KU Leuven
Fabrice Bureau: Liège University
Thomas Marichal: Liège University

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: Abstract Resident tissue macrophages (RTM) can fulfill various tasks during development, homeostasis, inflammation and repair. In the lung, non-alveolar RTM, called interstitial macrophages (IM), importantly contribute to tissue homeostasis but remain little characterized. Here we show, using single-cell RNA-sequencing (scRNA-seq), two phenotypically distinct subpopulations of long-lived monocyte-derived IM, i.e. CD206+ and CD206−IM, as well as a discrete population of extravasating CD64+CD16.2+ monocytes. CD206+ IM are peribronchial self-maintaining RTM that constitutively produce high levels of chemokines and immunosuppressive cytokines. Conversely, CD206−IM preferentially populate the alveolar interstitium and exhibit features of antigen-presenting cells. In addition, our data support that CD64+CD16.2+ monocytes arise from intravascular Ly-6Clo patrolling monocytes that enter the tissue at steady-state to become putative precursors of CD206−IM. This study expands our knowledge about the complexity of lung IM and reveals an ontogenic pathway for one IM subset, an important step for elaborating future macrophage-targeted therapies.

Date: 2019
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DOI: 10.1038/s41467-019-11843-0

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