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* Department of Gene and Cell Medicine, Icahn Research Institute, Mount Sinai School of Medicine, New York, NY 10029;
Stowers Medical Institute, Harvard Stem Cell Institute and Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138; and
Department of Internal Medicine, Clinic of the University of Regensburg, Regensburg, Germany
There are two major myeloid pulmonary dendritic cell (DC) populations: CD103+ DCs and CD11bhigh DCs. In this study, we investigated in detail the origins of both myeloid DC pools using multiple experimental approaches. We show that, in resting lung, Ly-6ChighCCR2high monocytes repopulated CD103+ DCs using a CCR2-dependent mechanism, and these DCs preferentially retained residual CCR2 in the lung, whereas, conversely, Ly-6ClowCCR2low monocytes repopulated CD11bhigh DCs. CX3CR1 was required to generate normal numbers of pulmonary CD11bhigh DCs, possibly because Ly-6Clow monocytes in the circulation, which normally express high levels of CX3CR1, failed to express bcl-2 and may have diminished survival in the circulation in the absence of CX3CR1. Overall, these data demonstrate that the two circulating subsets of monocytes give rise to distinct tissue DC populations.
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 work was supported by National Institutes of Health Grants AI49653 (to G.J.R.) and HL086899 and CA112100 (to M.M.), National Institutes of Health Postdoctoral Fellowships to C.J., F.T., and F.G., the German Research Foundation, and the Phillippe Foundation, respectively.
2 Current address: Medical Clinic III, University Hospital Aachen, 52074 Aachen, Germany.
3 Address correspondence and reprint requests to Dr. Gwendalyn J. Randolph, Department of Gene and Cell Medicine, 1425 Madison Avenue, Box 1496, New York, NY 10029. E-mail address: Gwendalyn.Randolph{at}mssm.edu
4 Abbreviations used in this paper: DC, dendritic cell; WT, wild type; BAL, bronchoalveolar lavage; MHC II, MHC class II.
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