PMID- 26464217 OWN - NLM STAT- MEDLINE DCOM- 20160527 LR - 20240210 IS - 1521-4141 (Electronic) IS - 0014-2980 (Print) IS - 0014-2980 (Linking) VI - 46 IP - 1 DP - 2016 Jan TI - Depletion of CD11c(+) cells in the CD11c.DTR model drives expansion of unique CD64(+) Ly6C(+) monocytes that are poised to release TNF-alpha. PG - 192-203 LID - 10.1002/eji.201545789 [doi] AB - 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-alpha following LPS stimulation. Thus, depletion of CD11c(+) cells induces expansion of a unique CD64(+) Ly6C(+) monocyte population poised to synthesize TNF-alpha. This finding will require consideration in experiments using depletion strategies to test the role of CD11c(+) DCs in immunity. CI - (c) 2015 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. FAU - Sivakumaran, Shivajanani AU - Sivakumaran S AD - Institute for Immunity and Transplantation, University College London, London, UK. AD - Cancer Institute, University College London, London, UK. FAU - Henderson, Stephen AU - Henderson S AD - Cancer Institute, University College London, London, UK. AD - Bill Lyons Informatics Centre, University College London, London, UK. FAU - Ward, Sophie AU - Ward S AD - Institute for Immunity and Transplantation, University College London, London, UK. AD - Cancer Institute, University College London, London, UK. FAU - Sousa, Pedro Santos E AU - Sousa PS AD - Institute for Immunity and Transplantation, University College London, London, UK. AD - Cancer Institute, University College London, London, UK. FAU - Manzo, Teresa AU - Manzo T AD - Institute for Immunity and Transplantation, University College London, London, UK. AD - Cancer Institute, University College London, London, UK. FAU - Zhang, Lei AU - Zhang L AD - Institute for Immunity and Transplantation, University College London, London, UK. AD - Cancer Institute, University College London, London, UK. FAU - Conlan, Thomas AU - Conlan T AD - Institute for Immunity and Transplantation, University College London, London, UK. AD - Cancer Institute, University College London, London, UK. FAU - Means, Terry K AU - Means TK AD - MGH Center for Immunology and Inflammatory Diseases, Harvard Medical School, Boston, MA, USA. FAU - D'Aveni, Maud AU - D'Aveni M AD - CNRS UMR 8147, Universite Paris Descartes, Faculte de Medecine, Hopital Necker, Paris, France. FAU - Hermine, Olivier AU - Hermine O AD - CNRS UMR 8147, Universite Paris Descartes, Faculte de Medecine, Hopital Necker, Paris, France. FAU - Rubio, Marie-Therese AU - Rubio MT AD - CNRS UMR 8147, Universite Paris Descartes, Faculte de Medecine, Hopital Necker, Paris, France. FAU - Chakraverty, Ronjon AU - Chakraverty R AD - Institute for Immunity and Transplantation, University College London, London, UK. AD - Cancer Institute, University College London, London, UK. FAU - Bennett, Clare L AU - Bennett CL AD - Institute for Immunity and Transplantation, University College London, London, UK. AD - Cancer Institute, University College London, London, UK. LA - eng GR - 20265/CRUK_/Cancer Research UK/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151130 PL - Germany TA - Eur J Immunol JT - European journal of immunology JID - 1273201 RN - 0 (Antigens, Ly) RN - 0 (CD11c Antigen) RN - 0 (Ly-6C antigen, mouse) RN - 0 (Receptors, IgG) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Animals MH - Antigens, Ly/immunology MH - CD11c Antigen/immunology MH - Dendritic Cells/*immunology MH - Flow Cytometry MH - Mice MH - Mice, Knockout MH - Mice, Transgenic MH - Monocytes/*cytology/*immunology MH - Oligonucleotide Array Sequence Analysis MH - Receptors, IgG/immunology MH - Tumor Necrosis Factor-alpha/*biosynthesis/immunology PMC - PMC4722854 OTO - NOTNLM OT - CD11c.DTR OT - Dendritic cells OT - Depletion OT - Diphtheria toxin receptor (DTR) OT - Monocytes OT - Monocytosis EDAT- 2015/10/16 06:00 MHDA- 2016/05/28 06:00 PMCR- 2016/01/22 CRDT- 2015/10/15 06:00 PHST- 2015/05/07 00:00 [received] PHST- 2015/09/10 00:00 [revised] PHST- 2015/10/07 00:00 [accepted] PHST- 2015/10/15 06:00 [entrez] PHST- 2015/10/16 06:00 [pubmed] PHST- 2016/05/28 06:00 [medline] PHST- 2016/01/22 00:00 [pmc-release] AID - 10.1002/eji.201545789 [doi] PST - ppublish SO - Eur J Immunol. 2016 Jan;46(1):192-203. doi: 10.1002/eji.201545789. Epub 2015 Nov 30.