Late-Breaking Abstract: A Lung-Resident Ly6c(+) Monocyte Proliferates To Give Rise To Immunosuppressive Lung Macrophages

Introduction: To ensure appropriate responses to foreign components present in the environment, the lung is endowed with an important network of immune cells. Among these cells, macrophages are tissue-resident phagocytes that play an essential role in the onset and the regulation of immune responses. If alveolar macrophages (AMs) were described decades ago, the last few years have seen the outcome of a new understanding of their ontogeny but also the characterization of a new macrophage subset, the interstitial macrophages (IMs). These discoveries highlight the complexity of the monocyte/macrophage axis in the lung. Yet, precise description of the whole monocyte/macrophage network in the lung is lacking. Materials and Methods: Lung-resident monocytes/macrophages were selected as F4/80+ tissue-resident cells using different approaches, such as intravenous injections of clodronate liposomes and fluorochrome-associated antibodies or immunohistochemistry. We studied their origin at the steady state and under stress condition using transgenic animals and bone marrow chimerism. To further assess their function, local stimulation with various TLR ligands were used. Results: In addition to AMs and IMs, we identified a Ly6c+ tissue-resident monocyte which does not derive from classical blood monocytes. Such tissue monocytes are able to proliferate in vivo upon stimulation with some, but not all TLR ligands to induce a new population of immunosuppressive lung macrophages. Conclusions: This study identifies the existence of a local pool of lung-resident monocytes able to proliferate and generate new immunosuppressive lung macrophages in response to specific environmental stimuli.