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Depletion of CD11c(+) cells in the CD11c.DTR model drives expansion of unique CD64(+) Ly6C(+) monocytes that are poised to release TNF-α

Sivakumaran, S; Henderson, S; Ward, S; Santos E Sousa, P; Manzo, T; Zhang, L; Conlan, T; ... Bennett, CL; + view all (2016) Depletion of CD11c(+) cells in the CD11c.DTR model drives expansion of unique CD64(+) Ly6C(+) monocytes that are poised to release TNF-α. European Journal of Immunology , 46 (1) pp. 192-203. 10.1002/eji.201545789. Green open access

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Abstract

Dendritic cells (DCs) play a vital role in innate and adaptive immunities. Inducible depletion of CD11c(+) DCs engineered to express a high-affinity diphtheria toxin receptor has been a powerful tool to dissect DC function in vivo. However, despite reports showing that loss of DCs induces transient monocytosis, the monocyte population that emerges and the potential impact of monocytes on studies of DC function have not been investigated. We found that depletion of CD11c(+) cells from CD11c.DTR mice induced the expansion of a variant CD64(+) Ly6C(+) monocyte population in the spleen and blood that was distinct from conventional monocytes. Expansion of CD64(+) Ly6C(+) monocytes was independent of mobilization from the BM via CCR2 but required the cytokine, G-CSF. Indeed, this population was also expanded upon exposure to exogenous G-CSF in the absence of DC depletion. CD64(+) Ly6C(+) monocytes were characterized by upregulation of innate signaling apparatus despite the absence of inflammation, and an increased capacity to produce TNF-α following LPS stimulation. Thus, depletion of CD11c(+) cells induces expansion of a unique CD64(+) Ly6C(+) monocyte population poised to synthesize TNF-α. This finding will require consideration in experiments using depletion strategies to test the role of CD11c(+) DCs in immunity.

Type: Article
Title: Depletion of CD11c(+) cells in the CD11c.DTR model drives expansion of unique CD64(+) Ly6C(+) monocytes that are poised to release TNF-α
Location: Germany
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/eji.201545789
Publisher version: http://dx.doi.org/10.1002/eji.201545789
Language: English
Additional information: © 2015 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: CD11c.DTR, Dendritic cells, Depletion, Diphtheria toxin receptor (DTR), Monocytes, Monocytosis
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: https://discovery.ucl.ac.uk/id/eprint/1473993
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