The Journal of Experimental Medicine
StemCell Technologies
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Published online December 26, 2006
doi:10.1084/jem.20061011
The Journal of Experimental Medicine, Vol. 204, No. 1, 171-180
The Rockefeller University Press, 0022-1007 $30.00
© 2006 Varol et al.
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ARTICLE

 Monocytes give rise to mucosal, but not splenic, conventional dendritic cells

Chen Varol1, Limor Landsman1, Darin K. Fogg3, Liat Greenshtein1, Boaz Gildor1, Raanan Margalit1, Vyacheslav Kalchenko2, Frederic Geissmann3, and Steffen Jung1

1 Department of Immunology and 2 Department of Veterinary Resources, The Weizmann Institute of Science, 76100 Rehovot, Israel
3 Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Mononuclear Phagocyte Biology, Necker Enfants Malades Institute, and University of Paris Rene Descartes Medical School, Necker Enfants Malades Hospital, 75015 Paris, France

CORRESPONDENCE Steffen Jung: s.jung{at}weizmann.ac.il

The mononuclear phagocyte (MP) system is a body-wide macrophage (M{Phi}) and dendritic cell (DC) network, which contributes to tissue homeostasis, inflammation, and immune defense. The in vivo origins of MPs remain poorly understood. Here, we use an adoptive precursor cell transfer strategy into MP-depleted mice to establish the in vivo differentiation sequence from a recently identified M{Phi}/DC-restricted bone marrow (BM) precursor (MDP) via BM and blood intermediates to peripheral M{Phi}s and DCs. We show that MDPs are in vivo precursors of BM and blood monocytes. Interestingly, grafted Gr1high "inflammatory" blood monocytes shuttle back to the BM in the absence of inflammation, convert into Gr1low monocytes, and contribute further to MP generation. The grafted monocytes give rise to DCs in the intestinal lamina propria and lung, but not to conventional CD11chigh DCs in the spleen, which develop during homeostasis from MDPs without a monocytic intermediate.

Abbreviations used: DTR, diphtheria toxin receptor; DTx, diphtheria toxin; IBC, intra bone cavity; lp, lamina propria; MDP, M{Phi}/DC precursor; MP, mononuclear phagocyte; M{Phi}, macrophage.


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