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Intrasplenic steady-state dendritic cell precursors that are distinct from monocytes

Abstract

Immediate precursors of the many subtypes of dendritic cells (DCs) remain obscure. Here we purified a splenic precursor population that produced all splenic CD8+ and CD8 conventional DCs (cDCs) but not plasmacytoid DCs or other lineages. This 'pre-cDC' population included cells 'precommitted' to form either CD8+ or CD8 cDCs. The pre-cDCs, which comprised 0.05% of splenocytes, expressed a CD11cintCD45RAloCD43intSIRP-αintCD4CD8 major histocompatibility complex class II–negative surface phenotype. The pre-cDCs were not monocytes. Monocytes generated few cDCs in steady-state recipient mice. However, when transferred into mice with an inflammatory milieu dependent on granulocyte-macrophage colony-stimulating factor, monocytes produced a distinct type of splenic DC. Thus, the inflammatory status of the host influences the developmental origin and type of DC present in lymphoid tissues.

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Figure 1: In vivo assay for splenic cDC precursor activity.
Figure 2: Purification of cDC precursors from spleen.
Figure 3: Characterization of pre-cDCs and their progeny.
Figure 4: CD24 expression on pre-cDCs segregates precursors of CD8+ and CD8 cDCs.
Figure 5: Morphology and phagocytic capacity of pre-cDCs versus Ly6Chi bone marrow monocytes.
Figure 6: Monocytes produce splenic DCs during inflammation.

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Acknowledgements

We thank K. Gray for animal husbandry; C. Young, C. Tarlinton, V. Milovac and J. Garbe for flow cytometry; S. Mifsud, L. Di Rago, B. Croker and M. Bradtke for technical assistance; and A. Roberts for discussions. Supported by the Cooperative Research Centre for Vaccine Technology (S.H.N.), the Australian Government (S.H.N.), Melbourne University (S.H.N.) and the Australian National Health and Medical Research Council (215203 to K.S.).

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Correspondence to Shalin H Naik or Ken Shortman.

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Supplementary information

Supplementary Fig. 1

In vivo assays for DC precursor positivity. (PDF 278 kb)

Supplementary Fig. 2

Protocol for isolation of pre-cDCs. (PDF 341 kb)

Supplementary Fig. 3

A model of splenic DC development from different precursors. (PDF 186 kb)

Supplementary Fig. 4

M-CSF responsiveness of pre-cDC and monocytes. (PDF 133 kb)

Supplementary Fig. 5

Monocyte isolation. (PDF 312 kb)

Supplementary Fig. 6

Monocyte recruitment during inflammation. (PDF 118 kb)

Supplementary Table 1

Surface phenotype of pre-cDC, cDC and pDC. (PDF 74 kb)

Supplementary Table 2

Lineage potential of pre-cDC and monocytes. (PDF 60 kb)

Supplementary Table 3

cDC precursor activity of BM monocytes and non-monocytes assayed day 10 after transfer. (PDF 49 kb)

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Naik, S., Metcalf, D., van Nieuwenhuijze, A. et al. Intrasplenic steady-state dendritic cell precursors that are distinct from monocytes. Nat Immunol 7, 663–671 (2006). https://doi.org/10.1038/ni1340

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