CSF1R regulates monocyte subset differentiation and intracellular metabolism.

Alexandre Gallerand; Johanna Merlin; Zakariya Caillot; Chloe Delaby; Elisa Bord; Jichang Han; Bastien Dolfi; Michael D. Chang; Guilhem R. Thierry; Alexia Castiglione; Sacha Grenet; Eloïse Goës; Maxime Franceschini; Gisèle Jarretou; Fairouz N. Zair; Evy Boré; Florian Tuffin; David Dombrowicz; Giulia Chinetti; Rodolphe Guinamard; Maxim N. Artyomov; Abdelilah Wakkach; Didier F. Pisani; Gwendalyn J. Randolph; Adeline Bertola; Patrick Auberger; Arnaud Jacquel; David Arthur Hume; Jesse W. Williams; Marc Bajénoff

doi:10.1038/s41467-026-75263-7

ImmunologyNature CommunicationsJul 4, 2026

Peer-reviewed journal article

CSF1R regulates monocyte subset differentiation and intracellular metabolism.

Alexandre Gallerand iD, Johanna Merlin iD, Zakariya Caillot, Chloe Delaby, Elisa Bord, Jichang Han iD, Bastien Dolfi iD, Michael D. Chang iD, Guilhem R. Thierry iD, Alexia Castiglione, Sacha Grenet iD, Eloïse Goës, Maxime Franceschini, Gisèle Jarretou iD, Fairouz N. Zair, Evy Boré, Florian Tuffin, David Dombrowicz iD, Giulia Chinetti iD, Rodolphe Guinamard iD, Maxim N. Artyomov iD, Abdelilah Wakkach iD, Didier F. Pisani iD, Gwendalyn J. Randolph iD, Adeline Bertola iD, , Stoyan Ivanov iD

Abstract

Monocytes are key circulating effectors of vascular homeostasis, innate immunity and inflammation. Following their generation in mouse bone marrow, classical (Ly6Chigh) monocytes are mobilized into the blood circulation where they mature into non-classical (Ly6Clow) 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 IL34. Here, we report that acute CSF1R blockade or genetic deletion negatively interferes with monocyte intracellular metabolism and reduces blood Ly6Clow monocytes in part by blunting differentiation of Ly6Chigh monocytes. Based upon lineage-specific deletion of GFPT1 (Glutamine-Fructose-6-Phosphate Transaminase 1), the hexosamine biosynthetic pathway (HBP) is identified as a novel regulator of CSF1R expression and monocyte subset diversity. Our findings provide new insights into the link between CSF1R signaling, metabolic regulation, and monocyte survival and differentiation.

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