The lifespan and kinetics of human dendritic cell subsets and their precursors in health and inflammation
: Lubin, Ruth; Patel, Amit A.; Mackerodt, Jonas; Zhang, Yan; Gvili, Rotem; Mulder, Kevin; Dutertre, Charles-Antoine; Jalali, Parinaaz; Glanville, James R. W.; Hazan, Idit; Sridharan, Nikhila; Rivkin, Gurion; Akarca, Ayse; Marafioti, Teresa; Gilroy, Derek W.; Kandel, Leonid; Mildner, Alexander; Wilensky, Asaf; Asquith, Becca; Ginhoux, Florent; Macallan, Derek; Yona, Simon
Publisher: ROCKEFELLER UNIV PRESS
: NEW YORK
: 2024
: Journal of Experimental Medicine
: J EXP MED
: e20220867
: 221
: 11
: 23
: 0022-1007
: 1540-9538
DOI: https://doi.org/10.1084/jem.20220867
: https://rupress.org/jem/article/221/11/e20220867/277031/The-lifespan-and-kinetics-of-human-dendritic-cell
: https://research.utu.fi/converis/portal/detail/Publication/459053574
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 similar to 2.16 days, while cDC1 and DC2 circulate for similar to 1.32 and similar to 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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S. Yona received a startup funding from the Hebrew University and is supported by the Israel Science Foundation Personal Grant (192/20) and Equipment Grant (316/20). A.A. Patel was supported by a PhD Studentship from the Engineering and Physical Sciences Research Council UK research council. R. Lubin is a scholar of the Ariane de Rothschild woman doctoral program. D. Macallan received funding from the Medical Research Council UK (G1001052), The Wellcome Trust (project grant 093053/Z/10/Z), Jefferiss Trust, and Bloodwise (15012). B. Asquith is a Wellcome Trust Investigator (103865). Inclusion and diversity statement: One or more of the authors of this paper received support from a program designed to increase minority representation in science.
