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Distinct Differentiation Potential of Blood Monocyte Subsets in the Lung¹

Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel

Peripheral blood monocytes are a population of circulating mononuclear phagocytes that harbor potential to differentiate into macrophages and dendritic cells. As in humans, monocytes in the mouse comprise two phenotypically distinct subsets that are Gr1^highCX₃CR1^int and Gr1^lowCX₃CR1^high, respectively. The question remains whether these populations contribute differentially to the generation of peripheral mononuclear phagocytes. In this study, we track the fate of adoptively transferred, fractionated monocyte subsets in the lung of recipient mice. We show that under inflammatory and noninflammatory conditions, both monocyte subsets give rise to pulmonary dendritic cells. In contrast, under the conditions studied, only Gr1^lowCX₃CR1^high monocytes, but not Gr1^highCX₃CR1^int cells, had the potential to differentiate into lung macrophages. However, Gr1^highCX₃CR1^int monocytes could acquire this potential upon conversion into Gr1^lowCX₃CR1^high cells. Our results therefore indicate an intrinsic dichotomy in the differentiation potential of the two main blood monocyte subsets.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This study was supported by the Minerva and the Pasteur-Weizmann Foundations. S.J. is the incumbent of the Pauline Recanati Career Development Chair and a scholar of the Benoziyo Center for Molecular Medicine.

² Address correspondence and reprint requests to Dr. Steffen Jung, Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel. E-mail address: s.jung{at}weizmann.ac.il

³ Abbreviations used in this paper: M, macrophage; DC, dendritic cell; BAL, bronchoalveolar lavage; BM, bone marrow; cDC, conventional CD11c^high DC; DTx, diphtheria toxin; DTR, DTx receptor; FKN, fractalkine; int, intermediate; i.t., intratracheal; LN, lymph node; wt, wild type.

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