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 

Our goal is to decipher the diversity, metabolic profile and functions of resident macrophages in BAT and adrenal glands.

A) Brown adipose tissue. Using single-cell RNA seq, we documented an impressive diversity in myeloid cell populations in BAT. We are working with Dr. M. Artyomov to define the developmental trajectory and metabolic configuration of each of these populations. Results obtained in this project were recently published in Nature Communications (Gallerand et al., 2021). We are currently investigating the functions of BAT macrophage subsets during tissue homeostasis and cold exposure. We developed and validated genetic models allowing to target selectively BAT macrophage subsets.

B) Adrenal Glands. The presence of F4/80+ cells was demonstrated in adrenal glands by a pioneering work in 1984. More recently, it was established that F4/80 expression was shared among several myeloid cell types including macrophages, monocytes, dendritic cells and eosinophils. Macrophages have been described in endocrine organs including pancreas, testis and ovaries. Using multiple complementary approaches, we documented the presence of several macrophage populations in adrenal glands. We observed a sex dimorphism in macrophage populations and showed that these cells are involved in the homeostasis of local hormone levels, in particular during stress exposure (Dolfi et al., Cell Reports 2022). We are currently collaborating with Dr. Jesse Williams (Minnesota, USA) on this topic.

Research axis 2

Metabolic control of myeloid cell functions in chronic inflammatory diseases. We aim to unravel the impact of glucose metabolism on myeloid cell functions during atherosclerosis and psoriasis.

A) Atherosclerosis. Immune cell dysregulation and chronic inflammation are major causes of atherosclerotic plaque development. Importantly, myeloid cell activation is paralleled by increased glucose utilization. However, the biological significance of increased glucose incorporation in atherosclerotic plaques and the immune cell type(s) accumulating this metabolite still need to be established.

B) Psoriasis. Additionally, we are investigating the role of glucose metabolism on dendritic cell migration and IL-23 production during psoriasis and its exacerbation by fatty acids. IL-23 production by conventional dendritic cells is dependent on metabolic fluxes. We aim to decipher whether modulating glucose entry into the pentose phosphate pathway might impact on DCs migration and IL-23 production.

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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