Cellules myéloïdes et métabolisme

Presentation of the team

Our research focuses on the metabolic control of myeloid cell (monocytes, macrophages and dendritic cells) functions in health and disease.

We are currently following two research axes. First, we aim to uncover the diversity, metabolic profile and functions of tissue resident macrophages. We recently described the myeloid cell diversity and monocyte contribution to brown adipose tissue (BAT) expansion (Gallerand et al. Nat Comm 2021). In a manuscript recently published in Cell Reports (Dolfi et al. 2022), we focused on adrenal gland macrophages. Second, we aim to define how glucose metabolism impacts on myeloid cell function during chronic inflammatory diseases (i.e. atherosclerosis and psoriasis). We are investigating how glucose metabolization through glycolysis and the pentose phosphate pathway modulates cell functions and the disease outcome.
 

Key Words

Monocytes
Macrophages
Dendritic Cells
Atherosclerosis
Psoriasis

Responsable

Stoyan Ivanov

RESEARCH PROJECTS

Research Axis 1: To define the diversity and functions of adipose tissue myeloid cells (A. Bertola/S. Ivanov)

Brown adipose tissue and subcutaneous adipose tissue are the two major thermogenic adipose tissues. They contain numerous and diverse immune cell populations. Macrophages are the numerically predominant immune cell type in these tissues. Our previous work demonstrated an important monocyte contribution to all macrophage populations in thermogenic adipose tissues that dilutes embryonically seeded macrophages. These newly recruited monocytes follow distinct differentiation trajectories and generate two major macrophage populations characterized by their high expression of CD206 or CD226. We aim to explore the functions of these macrophages and to explore how they affect tissue and systemic metabolism.

Collaboration: Marc Bajénoff (France), Elvira Mass (Germany), Daniele Lettiere-Barbato (Italy), Jesse Williams (USA), Pia Rantakari (Finland), Maxim Artyomov (USA)

Funding: ANR, UniCA, FRM, ENS Lyon

Research Axis 2: To define the impact of macrophage ontogeny on their functions  (A. Gallerand/S. Ivanov)

Macrophages (Mφ) are mononuclear phagocytes that play key roles in innate immunity and maintenance of tissue homeostasis. While the first Mφ develop during embryonic haematopoiesis, these cells are replaced by monocyte-derived Mφ over time at a rate that is tissue-specific. Embryonic and monocyte-derived Mφ display distinct transcriptomic signatures, and the latter were suggested to promote inflammation. Monocytes are generated in bone marrow via two independent developmental pathways, each depending on either granulocyte-monocyte precursors (GMP) or monocyte-dendritic cell precursors (MDP). Using fate-mapping models and state-of-the-art analytic methods (spectral flow cytometry, whole-mount microscopy, bulk and single-cell RNA sequencing), we aim to determine factors that regulate monocyte development, recruitment and differentiation to decipher the relative contribution of embryonic and monocyte-derived macrophages to health and disease.

Collaboration: Marc Dalod (France), Jesse Williams (USA), Pia Rantakari (Finland), Maxim Artyomov (USA)

Funding: ANR, UniCA

Research Axis 3: To investigate how intracellular metabolism shapes myeloid cell repertoire and functions (J.Neels/G. Chinetti/S.Ivanov)

The immunometabolism field highlighted that myeloid cell metabolic configuration changes in health and disease and that their rewiring could modulate disease outcome. This includes inflammation which has been generally associated with chronic metabolic diseases and cancer. A better knowledge of metabolic fluxes in myeloid cells could allow to rewire intracellular metabolism and will pave the way for future cell type specific medicine. Our team aims to develop innovative projects in the field of immunometabolism. We developed a large and very dynamic international network allowing us to benefit from state-of-the-art technologies (single-cell enzyme activity assay, monocyte specific PET/CT analysis, SCENITH, metabolic flux analysis), genetic models and expertise from leading scientists in the field. We aim to define how intracellular metabolism shapes myeloid cell functions during chronic inflammatory diseases such as atherosclerosis, obesity and psoriasis. More specifically, the role of glucose metabolism in monocyte/macrophage function is studied with a particular focus on its role in a recently identified direct contribution of macrophages to vascular calcification. Moreover, the contribution of the hexosamine biosynthetic pathway (HBP) in glucose metabolism in monocyte/macrophages and its role in their biology is also investigated.

Collaboration: David Dombrowicz (France), David Masson (France), Dominique Bazin (France), Yann Guerardel (France), David Hume (Australia), Peter Carmeliet (Belgium), Maxim Artyomov (USA)

Funding: ANR, ERA-NET, FdF, NPF (USA), UniCA, FRM

Team members

Team leader: IVANOV Stoyan, DR2, INSERM
Permanent members:
GUINAMARD Rodolphe, CRCN, CNRS
BERTOLA Adeline, CRCN, INSERM
CHINETTI Giulia PU-PH, Université Côte d'Azur, CHU
LAREYRE Fabien PH, CHU
NEELS Jaap CRCN, INSERM
RAFFORT Juliette PH, Chaire 3IA, Université Côte d'Azur, CHU
Non Permanent members:
BORE Evy IE, CNRS
BOUCHET Thalia IE, CNRS
GOES Eloise Doctorante, FRM, UniCA
GRENET Sacha Doctorant, ENS, UniCA
GALLERAND Alexandre Postdoc, Université Côte d'Azur
TUFFIN Florian IE, CNRS
 

Alumni
  • DOLFI Bastien (PhD student 2020-2024), Postdoctoral position, Lausanne, Switzerland.
  • ZAHIR Fairouz (PhD student 2021-2024).
Publications
  • Westermann F, Tuzlak S, Kreiner V, Ignacio A, Bejarano D, Bijnen M, Cecconi V, van Hove H, Wang H, Andreadou M, Litscher G, Sparano C, Fróis-Martins R, Gallerand A, Roussel E, Oberbichler L, Lindemann R, DeFeo D, Liu Z, Kipar A, LeibundGut-Landmann S, McCoy K, Nixon I, Bain CC, Schneider C, Ivanov S, Tugues S, Greter M, Ginhoux F, Schlitzer A, Emmerson E, Becher B. Adenophages are an atypical macrophage population in exocrine glands sustained by ILC2-derived GM-CSF. Nat Immunol. 2026 Jan;27(1):26-34. doi: 10.1038/s41590-025-02356-8.
  • Rousseau D, Bonnafous S, Soysouvanh F, Sarrail D, Bourinet M, Strazzulla A, Patouraux S, Borderie A, Dolfi B, Gallerand A, Farrugia MA, Orian-Rousseau V, Xu Y, Williams JW, Ivanov S, Tran A, Anty R, Luci C, Gual P. CD44 in myeloid cells is a major driver of liver inflammation and injury in alcohol-associated liver disease. Hepatology. 2025 Nov 1;82(5):1211-1228. doi: 10.1097/HEP.0000000000001232.
  • Halper J, Dolfi B, Ivanov S, Madel MB, Blin-Wakkach C. Macrophages and osteoclasts: similarity and divergence between bone phagocytes. Front Immunol. 2025 Oct 8;16:1683872. doi: 10.3389/fimmu.2025.1683872.
  • Mintz RL, Han J, Butka EG, Gallerand A, Kim A, Ning S, Yiew NKH, Wohltmann M, Zou W, Zhang N, Morris SA, Zinselmeyer BH, Randolph GJ. Adipocytes are dispensable in shaping the ovarian cancer tumor microenvironment in the omentum. bioRxiv [Preprint]. 2025 Oct 29:2025.10.28.685098. doi: 10.1101/2025.10.28.685098.
  • Gallerand A, Merlin J, Caillot Z, Delaby C, Bord E, Han J, Dolfi B, Castiglione A, Grenet S, Franceschini M, Jarretou G, Zair FN, Boré E, Tuffin F, Dombrowicz D, Guinamard RR, Randolph GJ, Bertola A, Auberger P, Jacquel A, Hume DA, Williams JW, Bajénoff M, Neels JG, Ivanov S. CSF1R regulates monocyte subset differentiation and intracellular metabolism. bioRxiv [Preprint]. 2025 Jul 21:2025.07.17.665275. doi: 10.1101/2025.07.17.665275.
  • Xu Y, Hillman H, Chang M, Barrow F, Ivanov S, Revelo XS, Williams JW. Identification of conserved and tissue-restricted transcriptional profiles for lipid associated macrophages. Commun Biol. 2025 Jun 23;8(1):953. doi: 10.1038/s42003-025-08387-z.
  • Gallerand A, Han J, Mintz RL, Chen J, Lee DD, Chan MM, Harmon TT, Lin X, Huckstep CG, Du S, Liu T, Kipnis J, Lavine KJ, Schilling JD, Morley SC, Zinselmeyer BH, Murphy KM, Randolph GJ. Tracing LYVE1+ peritoneal fluid macrophages unveils two paths to resident macrophage repopulation with differing reliance on monocytes. bioRxiv [Preprint]. 2025 Mar 19:2025.03.19.644175. doi: 10.1101/2025.03.19.644175.
  • Ninni A, Zaccaria F, Verteramo L, Sciarretta F, Silveira LS, Rosa-Neto JC, Carotti S, Nevi L, Grumati P, Patel S, Carrera G, Sgambato A, Lucchetti D, Colella F, Severi I, Senzacqua M, Giordano A, Bernardini S, Di Biagio C, Tortolici F, Rizzo G, Cochain C, Chiurchiù V, Ivanov S, Zhou B, Williams JW, Savage DB, Aquilano K, Lettieri-Barbato D. MACanalyzeR scRNAseq analysis tool reveals PPARγHIGH/GDF15HIGH lipid-associated macrophages facilitate thermogenic expansion in BAT. Nat Commun. 2025 May 31;16(1):5063. doi: 10.1038/s41467-025-60295-2.
2024
  • Gallerand A, Caillot Z, Terekhova M, Castiglione A, Leporati L, Giacchero M, Pilot T, Chang M, Dolfi B, Zair FN, Goës E, Bennetot A, Mlamla Z, Mass E, Ginhoux F, Voehringer D, Mack M, Dombrowicz D, Williams JW, Masson D, Artyomov MN, Bertola A, Ivanov S. CD226+ adipose tissue macrophages arise from MDP-derived monocytes and regulate lipid metabolism. bioRxiv [Preprint]. 2024 Dec 5:2024.12.03.626330. doi: 10.1101/2024.12.03.626330.
  • Gallerand A, Han J, Ivanov S, Randolph GJ. Mouse and human macrophages and their roles in cardiovascular health and disease. Nat Cardiovasc Res. 2024 Dec;3(12):1424-1437. doi: 10.1038/s44161-024-00580-3.
  • Gallerand A, Dolfi B, Stunault MI, Caillot Z, Castiglione A, Strazzulla A, Chen C, Heo GS, Luehmann H, Batoul F, Vaillant N, Dumont A, Pilot T, Merlin J, Zair FN, Gilleron J, Bertola A, Carmeliet P, Williams JW, Arguello RJ, Masson D, Dombrowicz D, Yvan-Charvet L, Doyen D, Haschemi A, Liu Y, Guinamard RR, Ivanov S. Glucose metabolism controls monocyte homeostasis and migration but has no impact on atherosclerosis development in mice. Nat Commun. 2024 Oct 19;15(1):9027. doi: 10.1038/s41467-024-53267-5.
  • Sciarretta F, Ninni A, Zaccaria F, Chiurchiù V, Bertola A, Karlinsey K, Jia W, Ceci V, Di Biagio C, Xu Z, Gaudioso F, Tortolici F, Tiberi M, Zhang J, Carotti S, Boudina S, Grumati P, Zhou B, Brestoff JR, Ivanov S, Aquilano K, Lettieri-Barbato D. Lipid-associated macrophages reshape BAT cell identity in obesity. Cell Rep. 2024 Jul 23;43(7):114447. doi: 10.1016/j.celrep.2024.114447.
  • Pisani DF, Lettieri-Barbato D, Ivanov S. Polyamine metabolism in macrophage-adipose tissue function and homeostasis. Trends Endocrinol Metab. 2024 Nov;35(11):937-950. doi: 10.1016/j.tem.2024.05.008.
  • Dolfi B, Gallerand A, Caillot Z, Castiglione A, Zair FN, Leporati L, Giacchero M, Goës E, Strazzulla A, Dombrowicz D, Guinamard RR, Bertola A, Ivanov S. Sex-specific impact of psychosocial stress on hematopoiesis and blood leukocytes. Eur J Immunol. 2024 Aug;54(8):e2350851. doi: 10.1002/eji.202350851.
  • Xu Y, Patterson MT, Dolfi B, Zhu A, Bertola A, Schrank PR, Gallerand A, Kennedy AE, Hillman H, Dinh L, Shekhar S, Tollison S, Bold TD, Ivanov S, Williams JW. Adrenal gland macrophages regulate glucocorticoid production through Trem2 and TGF-β. JCI Insight. 2024 Jun 13;9(14):e174746. doi:10.1172/jci.insight.174746.
  • Han J, Gallerand A, Erlich EC, Helmink BA, Mair I, Li X, Eckhouse SR, Dimou FM, Shakhsheer BA, Phelps HM, Chan MM, Mintz RL, Lee DD, Schilling JD, Finlay CM, Allen JE, Jakubzick CV, Else KJ, Onufer EJ, Zhang N, Randolph GJ. Human serous cavity macrophages and dendritic cells possess counterparts in the mouse with a distinct distribution between species. Nat Immunol. 2024 Jan;25(1):155-165. doi: 10.1038/s41590-023-01688-7.
2023
  • Patterson MT, et al. Trem2 promotes foamy macrophage lipid uptake and survival in atherosclerosis. Nat Cardiovasc Res. 2023 Nov;2(11):1015-1031. doi:10.1038/s44161-023-00354-3.
  • Moratal C, et al. An exploratory human study investigating the influence of type 2 diabetes on macrophage phenotype after myocardial infarction. Int J Cardiol Heart Vasc. 2023 Nov 19;49:101309. doi:10.1016/j.ijcha.2023.101309. 
  • Guilbaud E, et al. Cholesterol efflux pathways hinder KRAS-driven lung tumor progenitor cell expansion. Cell Stem Cell. 2023 Jun 1;30(6):800-817.e9. doi:10.1016/j.stem.2023.05.005.
  • Bertola A, et al. Adipocytes in their (CD)40s. Haematologica. 2023 Jul 1;108(7):1726-1728. doi: 10.3324/haematol.2022.282475.
  • Bertola A, et al. Immune cell involvement in brown adipose tissue functions. Discov Immunol. 2022 Oct 31;1(1):kyac007. doi:10.1093/discim/kyac007.
  • Neels JG, Gollentz C, Chinetti G. Macrophage death in atherosclerosis: potential role in calcification. Front Immunol. 2023 Jul 4;14:1215612. doi:10.3389/fimmu.2023.1215612.
  • Dolfi B, et al. Unravelling the sex-specific diversity and functions of adrenal gland macrophages. Cell Rep. 2022 Jun 14;39(11):110949. doi:10.1016/j.celrep.2022.110949.
  • Neels JG, Leftheriotis G, Chinetti G. Atherosclerosis Calcification: Focus on Lipoproteins. Metabolites. 2023 Mar 21;13(3):457. doi: 10.3390/metabo13030457. 
  • Larbret F, et al. Deubiquitinase Inhibitors Impair Leukemic Cell Migration Through Cofilin Oxidation and Alteration of Actin Reorganization. Front Pharmacol. 2022 Jan 7;12:778216. doi:10.3389/fphar.2021.778216.
2022
  • Bertola A, Gallerand A, Ivanov S. Immune cell involvement in brown adipose tissue functions. Discov Immunol. 2022 Oct 31;1(1):kyac007. doi:10.1093/discim/kyac007.
  • Rodrigues RM, et al. E-Selectin-Dependent Inflammation and Lipolysis in Adipose Tissue Exacerbate Steatosis-to-NASH Progression via S100A8/9. Cell Mol Gastroenterol Hepatol. 2022;13(1):151-171. doi: 10.1016/j.jcmgh.2021.08.002. 
  • Dolfi B, et al. Unravelling the sex-specific diversity and functions of adrenal gland macrophages. Cell Rep. 2022 Jun 14;39(11):110949. doi:10.1016/j.celrep.2022.110949. 
  • Larbret F, et al. Deubiquitinase Inhibitors Impair Leukemic Cell Migration Through Cofilin Oxidation and Alteration of Actin Reorganization. Front Pharmacol. 2022 Jan 7;12:778216. doi:10.3389/fphar.2021.778216.
  • Khatir W, et al. Identification of a circulating immunological signature predictive of response to immune checkpoint inhibitors in patients with advanced non-small cell lung cancer. Clin Transl Med. 2022 Aug;12(8):e1018. doi: 10.1002/ctm2.1018.
  • Chinetti G, et al. Diabetes-Induced Changes in Macrophage Biology Might Lead to Reduced Risk for Abdominal Aortic Aneurysm Development. Metabolites. 2022 Jan 29;12(2):128. doi: 10.3390/metabo12020128.
2021
  • Merlin J, et al. Non-canonical glutamine transamination sustains efferocytosis by coupling redox buffering to oxidative phosphorylation. Nat Metab. 2021 Oct;3(10):1313-1326. doi: 10.1038/s42255-021-00471-y. 
  • Gallerand A, et al. Brown adipose tissue monocytes support tissue expansion. Nat Commun. 2021 Sep 6;12(1):5255. doi: 10.1038/s41467-021-25616-1. 
  • Dolfi B, et al. Macrophage metabolic regulation in atherosclerotic plaque. Atherosclerosis. 2021 Oct;334:1-8. doi: 10.1016/j.atherosclerosis.2021.08.010. 
  • Cifarelli V, et al. Visceral obesity and insulin resistance associate with CD36 deletion in lymphatic endothelial cells. Nat Commun. 2021 Jun 7;12(1):3350. doi:10.1038/s41467-021-23808-3. 
  • Sencio V, et al. Influenza Virus Infection Impairs the Gut's Barrier Properties and Favors Secondary Enteric Bacterial Infection through Reduced Production of Short-Chain Fatty Acids. Infect Immun. 2021 Aug 16;89(9):e0073420. doi:10.1128/IAI.00734-20. 
  • Courjon J, et al. Heterogeneous NLRP3 inflammasome signature in circulating myeloid cells as a biomarker of COVID-19 severity. Blood Adv. 2021 Mar 9;5(5):1523-1534. doi: 10.1182/bloodadvances.2020003918. 
  • Dufies O, et al. Escherichia coli Rho GTPase-activating toxin CNF1 mediates NLRP3 inflammasome activation via p21-activated kinases-1/2 during bacteraemia in mice. Nat Microbiol. 2021 Mar;6(3):401-412. doi: 10.1038/s41564-020-00832-5. 
Collaborators

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Fundings

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