Fate Mapping via Ms4a3-Expression History Traces Monocyte-Derived Cells.

Cell

Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore; Translational Immunology Institute, SingHealt

Published: September 2019


Category Ranking

98%

Total Visits

921

Avg Visit Duration

2 minutes

Citations

20

Article Abstract

Most tissue-resident macrophage (RTM) populations are seeded by waves of embryonic hematopoiesis and are self-maintained independently of a bone marrow contribution during adulthood. A proportion of RTMs, however, is constantly replaced by blood monocytes, and their functions compared to embryonic RTMs remain unclear. The kinetics and extent of the contribution of circulating monocytes to RTM replacement during homeostasis, inflammation, and disease are highly debated. Here, we identified Ms4a3 as a specific gene expressed by granulocyte-monocyte progenitors (GMPs) and subsequently generated Ms4a3 reporter, Ms4a3, and Ms4a3 fate-mapping models. These models traced efficiently monocytes and granulocytes, but no lymphocytes or tissue dendritic cells. Using these models, we precisely quantified the contribution of monocytes to the RTM pool during homeostasis and inflammation. The unambiguous identification of monocyte-derived cells will permit future studies of their function under any condition.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cell.2019.08.009DOI Listing

Publication Analysis

Top Keywords

monocyte-derived cells
8
monocytes rtm
8
homeostasis inflammation
8
fate mapping
4
mapping ms4a3-expression
4
ms4a3-expression history
4
history traces
4
traces monocyte-derived
4
cells tissue-resident
4
tissue-resident macrophage
4

Similar Publications

Macrophages (MΦs) are integral cellular components responsible for immune response and tissue homeostasis. Evaluation of their pro-inflammatory (M1) and anti-inflammatory (M2) polarization states, along with their metabolic profiles, typically conducted via flow cytometry, is crucial for assessing the immune status of an organism. Traditional flow cytometry relies on extrinsic fluorescent labels, which may interfere with cellular function.

View Article and Find Full Text PDF

Zika virus (ZIKV) is a mosquito-borne flavivirus causing a major epidemic in the Americas in 2015. Dendritic cells (DCs) are leukocytes with key antiviral functions, but their role in ZIKV infection remains under investigation. While most studies have focused on the monocyte-derived subtype of DCs, less is known about conventional dendritic cells (cDCs), essential for the orchestration of antiviral adaptive immunity.

View Article and Find Full Text PDF

Dendritic Cells Induce Clec5a-mediated Immune Modulation in MPTP-induced Parkinson's Disease Mouse Model.

Front Biosci (Landmark Ed)

August 2025

Division of Life Sciences and Department of Life Science, Graduate School, CHA University, 13488 Seongnam-si, Gyeonggi-do, Republic of Korea.

Background: Parkinson's disease (PD) is characterized by a progressive decline in dopaminergic neurons within the substantia nigra (SN). Although its underlying cause has yet to be fully elucidated, accumulating evidence suggests that neuroinflammation contributes substantially to disease development. Treatment strategies targeting neuroinflammation could improve PD outcomes.

View Article and Find Full Text PDF

Intravascular hemolysis (IVH), a pathological process associated with various conditions, triggers inflammatory responses, yet the key molecular drivers of these responses are poorly defined, particularly within the vasculature. To explore the role of NLRP3 inflammasome- and caspase-1-dependent pathways in IVH-induced vascular dysfunction, we used models of acute and chronic IVH, alongside heme stimulation of endothelial cells, thereby isolating this disease mechanism from its etiological causes. IVH induced rapid inflammatory responses in C57BL/6J mice, including IL-1β release within 15 minutes, and NLRP3-dependent caspase-1 activation in circulating leukocytes.

View Article and Find Full Text PDF

Obesity is a known risk factor for diseases of the pancreas, including diabetes, pancreatic cancer and pancreatitis, but mechanisms remain unclear. To elucidate how obesity impacts pancreatic immune homeostasis, we performed spatial, transcriptomic and functional profiling of human pancreatic immune cells from obese and non-obese organ donors. Obesity was associated with higher density of tissue resident memory T-cells (TRM) in the exocrine pancreas which display high cytotoxic functions and aggregated around macrophages.

View Article and Find Full Text PDF