CSF1R regulates monocyte subset differentiation and intracellular metabolism
Abstract
Monocytes are key circulating effectors of vascular homeostasis, innate immunity and inflammation. Following their generation in mouse bone marrow, classical (Ly6C high ) monocytes are mobilized into the blood circulation where they mature into non-classical (Ly6C low ) patrolling monocytes or are recruited into peripheral tissues where they differentiate into tissue resident or inflammatory macrophages. Monocytes and macrophages express CSF1R (CD115), the receptor for lineage-specific growth factors CSF1 and IL-34. Here, we report that acute CSF1R blockade or genetic deletion negatively interferes with monocyte intracellular metabolism and reduces blood Ly6C low monocytes in part by blunting differentiation of Ly6C high monocytes. Based upon lineage-specific deletion of Glutamine-Fructose-6-Phosphate Transaminase 1 (GFPT1), the hexosamine biosynthetic pathway (HBP) is identified as an important regulator of CSF1R expression and monocyte subsets. Inhibition of receptor tyrosine kinases CSF1R and FLT3 rewires and partially impairs metabolic activity in human monocytes. Our findings provide insights into the link between CSF1R signaling, metabolic regulation, and monocyte survival and differentiation.
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BibTeX
@article{gallerand2026csf1r,
title = {{CSF1R regulates monocyte subset differentiation and intracellular metabolism}},
author = {Alexandre Gallerand and Johanna Merlin and Zakariya Caillot and Chloé Delaby and Elisa Bord and Jichang Han and Bastien Dolfi and Michael Chang and Guilhem Thierry and Alexia Castiglione and Sacha Grenet and Eloïse Goës and Maxime Franceschini and Gisèle Jarretou and Fairouz Zair and Evy Boré and Florian Tuffin and David Dombrowicz and Giulia Chinetti and Rodolphe Guinamard and Maxim Artyomov and Abdelilah Wakkach and Didier Pisani and Gwendalyn Randolph and Adeline Bertola and Patrick Auberger and Arnaud Jacquel and David Hume and Jesse Williams and Marc Bajénoff and Jaap Neels and Stoyan Ivanov},
journal = {Nature Communications},
year = {2026},
month = jul,
doi = {10.1038/s41467-026-75263-7},
url = {https://hal.science/hal-05775276v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - CSF1R regulates monocyte subset differentiation and intracellular metabolism
AU - Alexandre Gallerand
AU - Johanna Merlin
AU - Zakariya Caillot
AU - Chloé Delaby
AU - Elisa Bord
AU - Jichang Han
AU - Bastien Dolfi
AU - Michael Chang
AU - Guilhem Thierry
AU - Alexia Castiglione
AU - Sacha Grenet
AU - Eloïse Goës
AU - Maxime Franceschini
AU - Gisèle Jarretou
AU - Fairouz Zair
AU - Evy Boré
AU - Florian Tuffin
AU - David Dombrowicz
AU - Giulia Chinetti
AU - Rodolphe Guinamard
AU - Maxim Artyomov
AU - Abdelilah Wakkach
AU - Didier Pisani
AU - Gwendalyn Randolph
AU - Adeline Bertola
AU - Patrick Auberger
AU - Arnaud Jacquel
AU - David Hume
AU - Jesse Williams
AU - Marc Bajénoff
AU - Jaap Neels
AU - Stoyan Ivanov
PY - 2026
DA - 2026/07/04
JO - Nature Communications
DO - 10.1038/s41467-026-75263-7
UR - https://hal.science/hal-05775276v1
AB - Monocytes are key circulating effectors of vascular homeostasis, innate immunity and inflammation. Following their generation in mouse bone marrow, classical (Ly6C high ) monocytes are mobilized into the blood circulation where they mature into non-classical (Ly6C low ) patrolling monocytes or are recruited into peripheral tissues where they differentiate into tissue resident or inflammatory macrophages. Monocytes and macrophages express CSF1R (CD115), the receptor for lineage-specific growth factors CSF1 and IL-34. Here, we report that acute CSF1R blockade or genetic deletion negatively interferes with monocyte intracellular metabolism and reduces blood Ly6C low monocytes in part by blunting differentiation of Ly6C high monocytes. Based upon lineage-specific deletion of Glutamine-Fructose-6-Phosphate Transaminase 1 (GFPT1), the hexosamine biosynthetic pathway (HBP) is identified as an important regulator of CSF1R expression and monocyte subsets. Inhibition of receptor tyrosine kinases CSF1R and FLT3 rewires and partially impairs metabolic activity in human monocytes. Our findings provide insights into the link between CSF1R signaling, metabolic regulation, and monocyte survival and differentiation.
SN - 2041-1723
SN - 2041-1723
ER -