Dendritic cells (DC) are specialized mononuclear phagocytes that link innate and adaptive immunity. They comprise two principal subsets: plasmacytoid DC (pDC) and conventional DC (cDC). Understanding the generation, differentiation, and migration of cDC is critical for immune homeostasis. Through human in vivo deuterium-glucose labeling, we observed the rapid appearance of AXL+ Siglec6+ DC (ASDC) in the bloodstream. ASDC circulate for ∼2.16 days, while cDC1 and DC2 circulate for ∼1.32 and ∼2.20 days, respectively, upon release from the bone marrow. Interestingly, DC3, a cDC subset that shares several similarities with monocytes, exhibits a labeling profile closely resembling that of DC2. In a human in vivo model of cutaneous inflammation, ASDC were recruited to the inflammatory site, displaying a distinctive effector signature. Taken together, these results quantify the ephemeral circulating lifespan of human cDC and propose functions of cDC and their precursors that are rapidly recruited to sites of inflammation.
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4 November 2024
Article|
October 17 2024
The lifespan and kinetics of human dendritic cell subsets and their precursors in health and inflammation
Ruth Lubin
,
Ruth Lubin
*
(Data curation, Formal analysis, Investigation, Methodology, Project administration, Validation, Visualization, Writing - review & editing)
1The Institute of Biomedical and Oral Research, Faculty of Dental Medicine, Hebrew University, Jerusalem, Israel
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Amit A. Patel
,
Amit A. Patel
*
(Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Validation, Visualization)
2Division of Medicine,
University College London
, London, UK
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Jonas Mackerodt
,
Jonas Mackerodt
*
(Data curation, Formal analysis, Methodology, Software, Visualization, Writing - original draft, Writing - review & editing)
3Department of Infectious Disease, Imperial
College London
, London, UK
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Yan Zhang
,
Yan Zhang
(Investigation)
4
Institute for Infection and Immunity, St. George’s, University of London
, London, UK
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Rotem Gvili
,
Rotem Gvili
(Formal analysis, Investigation, Validation)
1The Institute of Biomedical and Oral Research, Faculty of Dental Medicine, Hebrew University, Jerusalem, Israel
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Kevin Mulder
,
Kevin Mulder
(Formal analysis)
5
Gustave Roussy Cancer Campus
, Villejuif, France
6
Institut National de la Santé Et de la Recherche Médicale (INSERM) U1015, Equipe Labellisée—Ligue Nationale Contre le Cancer
, Villejuif, France
7
Université Paris-Saclay
, Gif-sur-Yvette, France
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Charles-Antoine Dutertre
,
Charles-Antoine Dutertre
(Methodology, Supervision)
5
Gustave Roussy Cancer Campus
, Villejuif, France
6
Institut National de la Santé Et de la Recherche Médicale (INSERM) U1015, Equipe Labellisée—Ligue Nationale Contre le Cancer
, Villejuif, France
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Parinaaz Jalali
,
Parinaaz Jalali
(Investigation)
2Division of Medicine,
University College London
, London, UK
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James R.W. Glanville
,
James R.W. Glanville
(Data curation, Investigation, Methodology, Project administration, Resources)
2Division of Medicine,
University College London
, London, UK
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Idit Hazan
,
Idit Hazan
(Writing - review & editing)
1The Institute of Biomedical and Oral Research, Faculty of Dental Medicine, Hebrew University, Jerusalem, Israel
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Nikhila Sridharan
,
Nikhila Sridharan
(Investigation)
1The Institute of Biomedical and Oral Research, Faculty of Dental Medicine, Hebrew University, Jerusalem, Israel
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Gurion Rivkin
,
Gurion Rivkin
(Investigation, Resources)
8
Department of Orthopaedic Surgery, Hadassah-Hebrew University Medical Center
, Jerusalem, Israel
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Ayse Akarca
,
Ayse Akarca
(Investigation)
9
University College London
, London, UK
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Teresa Marafioti
,
Teresa Marafioti
(Methodology)
9
University College London
, London, UK
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Derek W. Gilroy
,
Derek W. Gilroy
(Investigation, Methodology, Resources)
2Division of Medicine,
University College London
, London, UK
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Leonid Kandel
,
Leonid Kandel
(Data curation, Project administration, Resources)
8
Department of Orthopaedic Surgery, Hadassah-Hebrew University Medical Center
, Jerusalem, Israel
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Alexander Mildner
,
Alexander Mildner
(Methodology, Resources, Writing - review & editing)
10MediCity Research Laboratory,
University of Turku
, Turku, Finland
11
InFLAMES Research Flagship, University of Turku
, Turku, Finland
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Asaf Wilensky
,
Asaf Wilensky
(Resources)
12Department of Periodontology, Faculty of Dental Medicine,
Hadassah Medical Center, Hebrew University of Jerusalem
, Jerusalem, Israel
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Becca Asquith
,
Becca Asquith
(Data curation, Formal analysis, Investigation, Methodology, Software, Supervision, Validation, Visualization, Writing - review & editing)
3Department of Infectious Disease, Imperial
College London
, London, UK
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Florent Ginhoux
,
Florent Ginhoux
(Resources)
5
Gustave Roussy Cancer Campus
, Villejuif, France
13
Singapore Immunology Network, Agency for Science, Technology and Research
, Singapore
14Department of Immunology and Microbiology,
Shanghai Institute of Immunology, Shanghai Jiao Tong, University School of Medicine
, Shanghai, China
15
Translational Immunology Institute, SingHealth Duke-NUS Academic Medical Centre
, Singapore
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Derek Macallan
,
Derek Macallan
(Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing)
4
Institute for Infection and Immunity, St. George’s, University of London
, London, UK
16
St. George’s University Hospitals NHS Foundation Trust
, London, UK
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Simon Yona
(Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Supervision, Visualization, Writing - original draft, Writing - review & editing)
1The Institute of Biomedical and Oral Research, Faculty of Dental Medicine, Hebrew University, Jerusalem, Israel
Correspondence to Simon Yona: [email protected]
Search for other works by this author on:
Ruth Lubin
Data curation, Formal analysis, Investigation, Methodology, Project administration, Validation, Visualization, Writing - review & editing
*
1The Institute of Biomedical and Oral Research, Faculty of Dental Medicine, Hebrew University, Jerusalem, Israel
Amit A. Patel
Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Validation, Visualization
*
2Division of Medicine,
University College London
, London, UK
Jonas Mackerodt
Data curation, Formal analysis, Methodology, Software, Visualization, Writing - original draft, Writing - review & editing
*
3Department of Infectious Disease, Imperial
College London
, London, UK
Yan Zhang
Investigation
4
Institute for Infection and Immunity, St. George’s, University of London
, London, UK
Rotem Gvili
Formal analysis, Investigation, Validation
1The Institute of Biomedical and Oral Research, Faculty of Dental Medicine, Hebrew University, Jerusalem, Israel
Kevin Mulder
Formal analysis
5
Gustave Roussy Cancer Campus
, Villejuif, France
6
Institut National de la Santé Et de la Recherche Médicale (INSERM) U1015, Equipe Labellisée—Ligue Nationale Contre le Cancer
, Villejuif, France
7
Université Paris-Saclay
, Gif-sur-Yvette, France
Charles-Antoine Dutertre
Methodology, Supervision
5
Gustave Roussy Cancer Campus
, Villejuif, France
6
Institut National de la Santé Et de la Recherche Médicale (INSERM) U1015, Equipe Labellisée—Ligue Nationale Contre le Cancer
, Villejuif, France
Parinaaz Jalali
Investigation
2Division of Medicine,
University College London
, London, UK
James R.W. Glanville
Data curation, Investigation, Methodology, Project administration, Resources
2Division of Medicine,
University College London
, London, UK
Idit Hazan
Writing - review & editing
1The Institute of Biomedical and Oral Research, Faculty of Dental Medicine, Hebrew University, Jerusalem, Israel
Nikhila Sridharan
Investigation
1The Institute of Biomedical and Oral Research, Faculty of Dental Medicine, Hebrew University, Jerusalem, Israel
Gurion Rivkin
Investigation, Resources
8
Department of Orthopaedic Surgery, Hadassah-Hebrew University Medical Center
, Jerusalem, Israel
Ayse Akarca
Investigation
9
University College London
, London, UK
Teresa Marafioti
Methodology
9
University College London
, London, UK
Derek W. Gilroy
Investigation, Methodology, Resources
2Division of Medicine,
University College London
, London, UK
Leonid Kandel
Data curation, Project administration, Resources
8
Department of Orthopaedic Surgery, Hadassah-Hebrew University Medical Center
, Jerusalem, Israel
Alexander Mildner
Methodology, Resources, Writing - review & editing
10MediCity Research Laboratory,
University of Turku
, Turku, Finland
11
InFLAMES Research Flagship, University of Turku
, Turku, Finland
Asaf Wilensky
Resources
12Department of Periodontology, Faculty of Dental Medicine,
Hadassah Medical Center, Hebrew University of Jerusalem
, Jerusalem, Israel
Becca Asquith
Data curation, Formal analysis, Investigation, Methodology, Software, Supervision, Validation, Visualization, Writing - review & editing
3Department of Infectious Disease, Imperial
College London
, London, UK
Florent Ginhoux
Resources
5
Gustave Roussy Cancer Campus
, Villejuif, France
13
Singapore Immunology Network, Agency for Science, Technology and Research
, Singapore
14Department of Immunology and Microbiology,
Shanghai Institute of Immunology, Shanghai Jiao Tong, University School of Medicine
, Shanghai, China
15
Translational Immunology Institute, SingHealth Duke-NUS Academic Medical Centre
, Singapore
Derek Macallan
Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing
4
Institute for Infection and Immunity, St. George’s, University of London
, London, UK
16
St. George’s University Hospitals NHS Foundation Trust
, London, UK
Simon Yona
Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Supervision, Visualization, Writing - original draft, Writing - review & editing
1The Institute of Biomedical and Oral Research, Faculty of Dental Medicine, Hebrew University, Jerusalem, Israel
Correspondence to Simon Yona: [email protected]
*
R. Lubin, A.A. Patel, and J. Mackerodt contributed equally to this paper.
Disclosures: The authors declare no competing interests exist.
Received:
May 17 2022
Revision Received:
July 16 2024
Accepted:
September 13 2024
Online ISSN: 1540-9538
Print ISSN: 0022-1007
Funder(s):
Israel Science Foundation
- Award Id(s): 192/20,316/20
Funder(s):
Engineering and Physical Sciences Research Council
Funder(s):
Medical Research Council
- Award Id(s): G1001052
Funder(s):
Jefferiss Trust
Funder(s):
Bloodwise
- Award Id(s): 15012
Funder(s):
Wellcome Trust
, Ariane de Rothschild woman doctoral program
- Award Id(s): ,093053/Z/10/Z,103865
Funder(s):
Hebrew University
© 2024 Lubin et al.
2024
Lubin et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Exp Med (2024) 221 (11): e20220867.
Article history
Received:
May 17 2022
Revision Received:
July 16 2024
Accepted:
September 13 2024
Citation
Ruth Lubin, Amit A. Patel, Jonas Mackerodt, Yan Zhang, Rotem Gvili, Kevin Mulder, Charles-Antoine Dutertre, Parinaaz Jalali, James R.W. Glanville, Idit Hazan, Nikhila Sridharan, Gurion Rivkin, Ayse Akarca, Teresa Marafioti, Derek W. Gilroy, Leonid Kandel, Alexander Mildner, Asaf Wilensky, Becca Asquith, Florent Ginhoux, Derek Macallan, Simon Yona; The lifespan and kinetics of human dendritic cell subsets and their precursors in health and inflammation. J Exp Med 4 November 2024; 221 (11): e20220867. doi: https://doi.org/10.1084/jem.20220867
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