» Articles » PMID: 39417994

The Lifespan and Kinetics of Human Dendritic Cell Subsets and Their Precursors in Health and Inflammation

Abstract

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.

References
1.
Naik S, Metcalf D, Van Nieuwenhuijze A, Wicks I, Wu L, OKeeffe M . Intrasplenic steady-state dendritic cell precursors that are distinct from monocytes. Nat Immunol. 2006; 7(6):663-71. DOI: 10.1038/ni1340. View

2.
Dutertre C, Becht E, Irac S, Khalilnezhad A, Narang V, Khalilnezhad S . Single-Cell Analysis of Human Mononuclear Phagocytes Reveals Subset-Defining Markers and Identifies Circulating Inflammatory Dendritic Cells. Immunity. 2019; 51(3):573-589.e8. DOI: 10.1016/j.immuni.2019.08.008. View

3.
Lee J, Breton G, Oliveira T, Zhou Y, Aljoufi A, Puhr S . Restricted dendritic cell and monocyte progenitors in human cord blood and bone marrow. J Exp Med. 2015; 212(3):385-99. PMC: 4354373. DOI: 10.1084/jem.20141442. View

4.
Patel A, Ginhoux F, Yona S . Monocytes, macrophages, dendritic cells and neutrophils: an update on lifespan kinetics in health and disease. Immunology. 2021; 163(3):250-261. PMC: 8207393. DOI: 10.1111/imm.13320. View

5.
Ginhoux F, Guilliams M, Merad M . Expanding dendritic cell nomenclature in the single-cell era. Nat Rev Immunol. 2022; 22(2):67-68. DOI: 10.1038/s41577-022-00675-7. View