The lifespan and kinetics of human dendritic cell subsets and their precursors in health and inflammation
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.
Authors
- Teresa Marafioti (ORCID: https://orcid.org/0000-0003-1223-6275)
- Yan Zhang (ORCID: https://orcid.org/0000-0001-6054-1309)
- Idit Hazan (ORCID: https://orcid.org/0000-0002-8431-0609)
- Derek C. Macallan (ORCID: https://orcid.org/0000-0002-3014-7148)
- Parinaaz Jalali
- Amit A. Patel (ORCID: https://orcid.org/0000-0003-4961-0347)
- Derek W. Gilroy (ORCID: https://orcid.org/0000-0003-3476-0844)
- James Glanville (ORCID: https://orcid.org/0000-0002-5653-3960)
- Charles‐Antoine Dutertre (ORCID: https://orcid.org/0000-0001-7950-3652)
- Ruth Lubin (ORCID: https://orcid.org/0000-0003-4077-7968)
- Leonid Kandel (ORCID: https://orcid.org/0000-0002-3760-7696)
- Florent Ginhoux (ORCID: https://orcid.org/0000-0002-2857-7755)
- Kevin Mulder (ORCID: https://orcid.org/0000-0002-1568-6581)
- Alexander Mildner (ORCID: https://orcid.org/0000-0002-2019-8427)
- Asaf Wilensky (ORCID: https://orcid.org/0000-0001-9002-6041)
- Becca Asquith (ORCID: https://orcid.org/0000-0002-5911-3160)
- Jonas Mackerodt (ORCID: https://orcid.org/0000-0002-2044-179X)
- Simon Yona (ORCID: https://orcid.org/0000-0002-3984-2008)
- Ayse U. Akarca (ORCID: https://orcid.org/0000-0003-0629-3927)
- Gurion Rivkin (ORCID: https://orcid.org/0000-0002-6825-3966)
- Rotem Gvili
- Nikhila Sridharan
Institutions
- Agency for Science, Technology and Research (SG)
- Inserm (FR)
- University of Turku (FI)
- St George's, University of London (GB)
- Shanghai Jiao Tong University (CN)
- Hebrew University of Jerusalem (IL)
- Université Paris-Saclay (FR)
- Hadassah Medical Center (IL)
- Singapore Immunology Network (SG)
- St George’s University Hospitals NHS Foundation Trust (GB)
- Institut Gustave Roussy (FR)
- University Medical Center (US)
- La Ligue Contre le Cancer (FR)
- SingHealth Duke-NUS Academic Medical Centre (SG)
- Institute of Immunology (HR)
- University College London (GB)
- Imperial College London (GB)
Publication Details
- Journal
- The Journal of Experimental Medicine
- Published
- 2024-10-17
- DOI
- https://doi.org/10.1084/jem.20220867
- Citations
- 24
- Primary Topic
- Immunotherapy and Immune Responses
- Type
- article
- Field-Weighted Citation Impact
- 5.77
Funders
- Wellcome Trust
- Hadassah Medical Organization
- Hebrew University of Jerusalem
- Israel Science Foundation
- Bloodwise
- Medical Research Council
- Engineering and Physical Sciences Research Council