α-ketoglutarate orchestrates macrophage activation through metabolic and epigenetic reprogramming
Open accessAbstract
Glutamine metabolism provides synergistic support for macrophage activation and elicitation of desirable immune responses; however, the underlying mechanisms regulated by glutamine metabolism to orchestrate macrophage activation remain unclear. Here we show that the production of α-ketoglutarate (αKG) via glutaminolysis is important for alternative (M2) activation of macrophages, including engagement of fatty acid oxidation (FAO) and Jmjd3-dependent epigenetic reprogramming of M2 genes. This M2-promoting mechanism is further modulated by a high αKG/succinate ratio, whereas a low ratio strengthens the proinflammatory phenotype in classically activated (M1) macrophages. As such, αKG contributes to endotoxin tolerance after M1 activation. This study reveals new mechanistic regulations by which glutamine metabolism tailors the immune responses of macrophages through metabolic and epigenetic reprogramming.
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In macrophage cells, α-KG produced via glutaminolysis promotes M2 activation via Jmjd3-dependent metabolic and epigenetic reprogramming.
“In macrophage cells, α-KG produced via glutaminolysis promotes M2 activation via Jmjd3-dependent metabolic and epigenetic reprogramming108.”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [108]
Macrophages are the gatekeepers of intestinal immune homeostasis, M1 macrophages elicit rapid proinflammatory responses to infection and tissue damage.
“Macrophages are the gatekeepers of intestinal immune homeostasis, M1 macrophages elicit rapid proinflammatory responses to infection and tissue damage.46 47”
Glutamine metabolism in TAMs promotes an M2 phenotype via the production of α-ketoglutarate, which aids in fatty acid oxidation and epigenetic activation of M2 genes.
“Glutamine metabolism in TAMs also promotes an M2 phenotype via the production of α‐ketoglutarate, which aids in fatty acid oxidation and epigenetic activation of M2 genes [235].”
From Tumor microenvironment signaling and therapeutics in cancer progression (2023) · cites this paper as [235]
Cites
Macrophage activation and polarization: nomenclature and experimental guidelines
Murray, P. J., Allen, J. E., Biswas, S. K., Fisher, E. A., Gilroy, D. W., Goerdt, S., Gordon, S., Hamilton, J. A., Ivashkiv, L. B., Lawrence, T., et al. (2014) · Immunity · doi:10.1016/j.immuni.2014.06.008 · Cited by 6,337 · see citing works
Chen, X., Xiu, M., Xing, J., Yu, S., Min, D., & Guo, F. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000479439 · Cited by 5,759 · see citing works
Succinate is an inflammatory signal that induces IL-1β through HIF-1α
Tannahill, G. M., Curtis, A. M., Adamik, J., Palsson-McDermott, E. M., McGettrick, A. F., Goel, G., Frezza, C., Bernard, N. J., Kelly, B., Foley, N. H., et al. (2013) · Nature · doi:10.1038/nature11986 · Cited by 4,176 · see citing works
A guide to immunometabolism for immunologists
O'Neill, L. A. J., Kishton, R. J., & Rathmell, J. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2016.70 · Cited by 3,315 · see citing works
Mills, E. L., Kelly, B., Logan, A., Costa, A. S. H., Varma, M., Bryant, C. E., Tourlomousis, P., Däbritz, J. H. M., Gottlieb, E., Latorre, I., et al. (2016) · Cell · doi:10.1016/j.cell.2016.08.064 · Cited by 2,291 · see citing works
From Krebs to clinic: glutamine metabolism to cancer therapy
Altman, B. J., Stine, Z. E., & Dang, C. V. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.71 · Cited by 2,119 · see citing works
Jha, A. K., Huang, S. C.-C., Sergushichev, A., Lampropoulou, V., Ivanova, Y., Loginicheva, E., Chmielewski, K., Stewart, K. M., Ashall, J., Everts, B., et al. (2015) · Immunity · doi:10.1016/j.immuni.2015.02.005 · Cited by 2,066 · see citing works
CRISPR-Cas9 Knockin Mice for Genome Editing and Cancer Modeling
Platt, R. J., Chen, S., Zhou, Y., Yim, M. J., Swiech, L., Kempton, H. R., Dahlman, J. E., Parnas, O., Eisenhaure, T. M., Jovanovic, M., et al. (2014) · Cell · doi:10.1016/j.cell.2014.09.014 · Cited by 2,001 · see citing works
Glutamine addiction: a new therapeutic target in cancer
Wise, D. R., & Thompson, C. B. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.05.003 · Cited by 1,770 · see citing works
Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity
Saeed, S., Quintin, J., Kerstens, H. H. D., Rao, N. A., Aghajanirefah, A., Matarese, F., Cheng, S.-C., Ratter, J., Berentsen, K., van der Ent, M. A., et al. (2014) · Science · doi:10.1126/science.1251086 · Cited by 1,761 · see citing works
Immunometabolism governs dendritic cell and macrophage function
O'Neill, L., & Pearce, E. (2016) · Journal of Experimental Medicine · doi:10.1084/jem.20151570 · Cited by 1,641 · see citing works
Macrophages, innate immunity and cancer: balance, tolerance, and diversity
Mantovani, A., & Sica, A. (2010) · Current Opinion in Immunology · doi:10.1016/j.coi.2010.01.009 · Cited by 1,484 · see citing works
Oxidative metabolism and PGC-1β attenuate macrophage-mediated inflammation
Vats, D., Mukundan, L., Odegaard, J. I., Zhang, L., Smith, K. L., Morel, C. R., Greaves, D. R., Murray, P. J., & Chawla, A. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.05.011 · Cited by 1,369 · see citing works
Endotoxin tolerance: new mechanisms, molecules and clinical significance
Biswas, S. K., & Lopez-Collazo, E. (2009) · Trends in Immunology · doi:10.1016/j.it.2009.07.009 · Cited by 1,318 · see citing works
Histone Lysine Methylation Dynamics: Establishment, Regulation, and Biological Impact
Black, J. C., Rechem, C. V., & Whetstine, J. R. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.11.006 · Cited by 1,318 · see citing works
Cell-intrinsic lysosomal lipolysis is essential for alternative activation of macrophages
Huang, S. C., Everts, B., Ivanova, Y., O’Sullivan, D., Nascimento, M., Smith, A. M., Beatty, W. L., Love-Gregory, L. D., Lam, W. Y., O’Neill, C. M., et al. (2014) · Nature Immunology · doi:10.1038/ni.2956 · Cited by 1,215 · see citing works
Satoh, T., Takeuchi, O., Vandenbon, A., Yasuda, K., Tanaka, Y., Kumagai, Y., Miyake, T., Matsushita, K., Okazaki, T., Saitoh, T., et al. (2010) · Nature Immunology · doi:10.1038/ni.1920 · Cited by 1,156 · see citing works
Rodríguez-Prados, J.-C., Través, P. G., Cuenca, J., Rico, D., Aragonés, J., Martín-Sanz, P., Cascante, M., & Boscá, L. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0901698 · Cited by 1,022 · see citing works
Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells
Carey, B. W., Finley, L. W. S., Cross, J. R., Allis, C. D., & Thompson, C. B. (2015) · Nature · doi:10.1038/nature13981 · Cited by 1,007 · see citing works
A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response
Kruidenier, L., Chung, C.-W., Cheng, Z., Liddle, J., Che, K., Joberty, G., Bantscheff, M., Bountra, C., Bridges, A., Diallo, H., et al. (2012) · Nature · doi:10.1038/nature11262 · Cited by 950 · see citing works
Arts, R. J. W., Novakovic, B., ter Horst, R., Carvalho, A., Bekkering, S., Lachmandas, E., Rodrigues, F., Silvestre, R., Cheng, S.-C., Wang, S.-Y., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.10.008 · Cited by 930 · see citing works
Bricker, D. K., Taylor, E. B., Schell, J. C., Orsak, T., Boutron, A., Chen, Y.-C., Cox, J. E., Cardon, C. M., Van Vranken, J. G., Dephoure, N., et al. (2012) · Science · doi:10.1126/science.1218099 · Cited by 843 · see citing works
Tet2 is required to resolve inflammation by recruiting Hdac2 to specifically repress IL-6
Zhang, Q., Zhao, K., Shen, Q., Han, Y., Gu, Y., Li, X., Zhao, D., Liu, Y., Wang, C., Zhang, X., et al. (2015) · Nature · doi:10.1038/nature15252 · Cited by 807 · see citing works
Self-citation“Re-educating” tumor-associated macrophages by targeting NF-κB
Hagemann, T., Lawrence, T., McNeish, I., Charles, K. A., Kulbe, H., Thompson, R. G., Robinson, S. C., & Balkwill, F. R. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20080108 · Cited by 792 · see citing works
Cummins, E. P., Berra, E., Comerford, K. M., Ginouves, A., Fitzgerald, K. T., Seeballuck, F., Godson, C., Nielsen, J. E., Moynagh, P., Pouyssegur, J., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0602235103 · Cited by 788 · see citing works
Broad defects in the energy metabolism of leukocytes underlie immunoparalysis in sepsis
Cheng, S.-C., Scicluna, B. P., Arts, R. J. W., Gresnigt, M. S., Lachmandas, E., Giamarellos-Bourboulis, E. J., Kox, M., Manjeri, G. R., Wagenaars, J. A. L., Cremer, O. L., et al. (2016) · Nature Immunology · doi:10.1038/ni.3398 · Cited by 637 · see citing works
mTORC2-IRF4 mediated metabolic reprograming is essential for macrophage alternative activation
Huang, S., Smith, A., Everts, B., Colonna, M., Pearce, E. L., Schilling, J., & Pearce, E. J. (2016) · Immunity · doi:10.1016/j.immuni.2016.09.016 · Cited by 579 · see citing works
Epigenetic regulation of the alternatively activated macrophage phenotype
Ishii, M., Wen, H., Corsa, C. A. S., Liu, T., Coelho, A. L., Allen, R., Carson, W. F., Cavassani, K. A., Li, X., Lukacs, N. W., et al. (2009) · Blood · doi:10.1182/blood-2009-04-217620 · Cited by 496 · see citing works
Self-citationMacrophage activation syndrome: a potentially fatal complication of rheumatic disorders
Sawhney, S. (2001) · Archives of Disease in Childhood · doi:10.1136/adc.85.5.421 · Cited by 469 · see citing works
Akt-mTORC1 signaling regulates Acly to integrate metabolic input to control of macrophage activation
Covarrubias, A. J., Aksoylar, H., Yu, J., Snyder, N. W., Worth, A. J., Iyer, S. S., Wang, J., Ben‐Sahra, I., Byles, V., Polynne-Stapornkul, T., et al. (2016) · eLife · doi:10.7554/elife.11612 · Cited by 455 · see citing works
Jmjd3 contributes to the control of gene expression in LPS‐activated macrophages
Santa, F. D., Narang, V., Yap, Z. H., Tusi, B. K., Burgold, T., Austenaa, L. M. I., Bucci, G., Cagánová, M., Notarbartolo, S., Casola, S. S., et al. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.271 · Cited by 422 · see citing works
Shalova, I. N., Lim, J. Y., Chittezhath, M., Zinkernagel, A. S., Beasley, F. C., Hernández-Jiménez, E., Toledano, V., Cubillos‐Zapata, C., Rapisarda, A., Chen, J., et al. (2015) · Immunity · doi:10.1016/j.immuni.2015.02.001 · Cited by 412 · see citing works
Epigenetic regulation of macrophage polarization and function
Ivashkiv, L. B. (2012) · Trends in Immunology · doi:10.1016/j.it.2012.11.001 · Cited by 396 · see citing works
Reductive glutamine metabolism is a function of the α-ketoglutarate to citrate ratio in cells
Fendt, S.-M., Bell, E. L., Keibler, M. A., Olenchock, B. A., Mayers, J. R., Wasylenko, T. M., Vokes, N. I., Guarente, L., Heiden, M. G. V., & Stephanopoulos, G. (2013) · Nature Communications · doi:10.1038/ncomms3236 · Cited by 364 · see citing works
Self-citationInhibition of oxygen sensors as a therapeutic strategy for ischaemic and inflammatory disease
Fraisl, P., Aragonés, J., & Carmeliet, P. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2761 · Cited by 326 · see citing works
Interferon-γ regulates cellular metabolism and mRNA translation to potentiate macrophage activation
Su, X., Yu, Y., Zhong, Y., Giannopoulou, E. G., Hu, X., Liu, H., Cross, J. R., Rätsch, G., Rice, C. M., & Ivashkiv, L. B. (2015) · Nature Immunology · doi:10.1038/ni.3205 · Cited by 298 · see citing works
Macrophage skewing by Phd2 haplodeficiency prevents ischaemia by inducing arteriogenesis
Takeda, Y., Costa, S., Delamarre, E., Roncal, C., de Oliveira, R. L., Squadrito, M. L., Finisguerra, V., Deschoemaeker, S., Bruyére, F., Wenes, M., et al. (2011) · Nature · doi:10.1038/nature10507 · Cited by 287 · see citing works
Self-citationα-Ketoglutarate Accelerates the Initial Differentiation of Primed Human Pluripotent Stem Cells
TeSlaa, T., Chaikovsky, A. C., Lipchina, I., Escobar, S. L., Hochedlinger, K., Huang, J., Graeber, T. G., Braas, D., & Teitell, M. A. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.07.002 · Cited by 287 · see citing works
Breast Cancer-Derived Lung Metastases Show Increased Pyruvate Carboxylase-Dependent Anaplerosis
Christen, S., Lorendeau, D., Schmieder, R., Broekaert, D., Metzger, K., Veys, K., Elia, I., Buescher, J. M., Orth, M. F., Davidson, S. M., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.09.042 · Cited by 258 · see citing works
Self-citationOxygen Sensing by T Cells Establishes an Immunologically Tolerant Metastatic Niche
Clever, D. C., Roychoudhuri, R., Constantinides, M. G., Askenase, M. H., Sukumar, M., Klebanoff, C. A., Eil, R. L., Hickman, H. D., Yu, Z., Pan, J. H., et al. (2016) · Cell · doi:10.1016/j.cell.2016.07.032 · Cited by 242 · see citing works
Liu, L., Lu, Y., Martinez, J., Bi, Y., Lian, G., Wang, T., Milasta, S., Wang, J., Yang, M., Liu, G., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1518000113 · Cited by 239 · see citing works
IFN-γ abrogates endotoxin tolerance by facilitating Toll-like receptor-induced chromatin remodeling
Chen, J., & Ivashkiv, L. B. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1007816107 · Cited by 154 · see citing works
del Fresno, C., Otero, K., Gómez-Garcı́a, L., González-León, M. C., Rangel, L. S., Fuentes‐Prior, P., Escoll, P., Baos, R., Caveda, L., García, F., et al. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.5.3032 · Cited by 149 · see citing works
Ho, P., Tsui, Y.-C., Feng, X., Greaves, D. R., & Wei, L. (2012) · Nature Immunology · doi:10.1038/ni.2238 · Cited by 108 · see citing works
Self-citationR-2-Hydroxyglutarate as the Key Effector of IDH Mutations Promoting Oncogenesis
Ye, D., Ma, S., Xiong, Y., & Guan, K. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.03.005 · Cited by 83 · see citing works
Jmjd3-Mediated H3K27me3 Dynamics Orchestrate Brown Fat Development and Regulate White Fat Plasticity
Pan, D., Huang, L., Zhu, L. J., Zou, T., Ou, J., Zhou, W., & Wang, Y. (2015) · Developmental Cell · doi:10.1016/j.devcel.2015.11.002 · Cited by 82 · see citing works
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Netea, M. G., Domínguez-Andrés, J., Barreiro, L. B., Chavakis, T., Divangahi, M., Fuchs, E., Joosten, L. A. B., van der Meer, J. W. M., Mhlanga, M. M., Mulder, W. J. M., et al. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-020-0285-6 · Cited by 2,690 · see citing works
Yunna, C., Mengru, H., Lei, W., & Weidong, C. (2020) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2020.173090 · Cited by 2,454 · see citing works
Orecchioni, M., Ghosheh, Y., Pramod, A. B., & Ley, K. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01084 · Cited by 2,063 · see citing works
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Macrophages and metabolism in the tumor microenvironment
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Yoo, H. C., Yu, Y. C., Sung, Y., & Han, J. M. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-00504-8 · Cited by 1,021 · see citing works
Identification of bioactive metabolites using activity metabolomics
Rinschen, M. M., Ivanisevic, J., Giera, M., & Siuzdak, G. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0108-4 · Cited by 1,008 · see citing works
Self-citationMetabolites and the Tumour Microenvironment: From Cellular Mechanisms to Systemic Metabolism
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Wang, L., Tang, L., Feng, Y., Zhao, S., Han, M., Zhang, C., Yuan, G., Zhu, J., Cao, S., Wu, Q., et al. (2020) · Gut · doi:10.1136/gutjnl-2019-320105 · Cited by 630 · see citing works
Macrophage de novo NAD+ synthesis specifies immune function in aging and inflammation
Minhas, P. S., Liu, L., Moon, P. K., Joshi, A. U., Dove, C., Mhatre, S., Contrepois, K., Wang, Q., Lee, B. A., Coronado, M., et al. (2019) · Nature Immunology · doi:10.1038/s41590-018-0255-3 · Cited by 501 · see citing works
Zhang, S., Weinberg, S., DeBerge, M., Gainullina, A., Schipma, M., Kinchen, J. M., Ben-Sahra, I., Gius, D. R., Yvan-Charvet, L., Chandel, N. S., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2018.12.004 · Cited by 485 · see citing works
Oh, M.-H., Sun, I.-H., Zhao, L., Leone, R. D., Sun, I.-M., Xu, W., Collins, S. L., Tam, A. J., Blosser, R. L., Patel, C. H., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci131859 · Cited by 456 · see citing works
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Cruzat, V., Macedo Rogero, M., Noel Keane, K., Curi, R., & Newsholme, P. (2018) · doi:10.20944/preprints201809.0459.v1 · Cited by 1,261 · see citing works
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Wilson, J. L., Nägele, T., Linke, M., Demel, F., Fritsch, S. D., Mayr, H. K., Cai, Z., Katholnig, K., Sun, X., Fragner, L., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.01.011 · Cited by 97 · see citing works
Yuan, Y., Xu, P., Jiang, Q., Cai, X., Wang, T., Peng, W., Sun, J., Zhu, C., Zhang, C., Yue, D., et al. (2020) · The EMBO Journal · doi:10.15252/embj.2019103304 · Cited by 92 · see citing works
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Lin, X.-F., Cui, X.-N., Yang, J., Jiang, Y.-F., Wei, T.-J., Xia, L., Liao, X.-Y., Li, F., Wang, D.-D., Li, J., et al. (2024) · Acta Pharmacologica Sinica · doi:10.1038/s41401-024-01389-3 · Cited by 69 · see citing works
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Nakanishi, T., & Kuragano, T. (2024) · Clinical Kidney Journal · doi:10.1093/ckj/sfae051 · Cited by 39 · see citing works
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Ferreira, C., Mesquita, I., Barbosa, A. M., Osório, N. S., Torrado, E., Beauparlant, C.-J., Droit, A., Cunha, C., Carvalho, A., Saha, B., et al. (2020) · PLOS Neglected Tropical Diseases · doi:10.1371/journal.pntd.0008125 · Cited by 35 · see citing works
Zhang, N., Sun, L., Zhou, S., Ji, C., Cui, T., Chu, Q., Ye, J., Liang, S., Ma, K., Liu, Y., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-58429-7 · Cited by 34 · see citing works
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Liu, H., Yin, G., Franco Leonardi, B., Lan, T., Ait Ahmed, Y., Berger, H., Kohlhepp, M. S., Amiridze, N., Martagón Calderón, N., Frau, C., et al. (2025) · Gut · doi:10.1136/gutjnl-2024-334425 · Cited by 23 · see citing works
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Sanchez Vasquez, J. D., Nkongolo, S., Traum, D., Sotov, V., Kim, S. C., Mahamed, D., Mehrotra, A., Patel, A., Chen, D. Y., Fung, S., et al. (2025) · Journal of Clinical Investigation · doi:10.1172/jci175241 · Cited by 11 · see citing works
- Authors
- Liu, P.-S., Wang, H., Li, X., Chao, T., Teav, T., Christen, S., Di Conza, G., Cheng, W.-C., Chou, C.-H., Vavakova, M., Muret, C., Debackere, K., Mazzone, M., Huang, H.-D., Fendt, S.-M., Ivanisevic, J., & Ho, P.-C.
- Affiliations
- University of Lausanne (CH)
- VIB-KU Leuven Center for Cancer Biology (BE)
- National Yang Ming Chiao Tung University (TW)
- KU Leuven (BE)
- Corresponding author
- Ho, Ping-Chih
- ORCID
- Venue
- Nature Immunology
- Published
- 2017-07-17
- Volume
- 18
- Issue
- 9
- Pages
- 985-994
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2735344772
- Cited by
- 1,264
- References
- 46
- Citations by year
- 2026: 210 · 2025: 213 · 2024: 192 · 2023: 153 · 2022: 144 · 2021: 125 · 2020: 110 · 2019: 62 · 2018: 45 · 2017: 10
- FWCI
- 28.34
- Type
- journal article
- Language
- en
- Open access
- green
- lirias.kuleuven.be
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Lirias (KU Leuven) (submittedVersion, other-oa)
- SERVAL (Université de Lausanne) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- alpha-ketoglutarate, glutamine metabolism, glutaminolysis, macrophage activation, M2 macrophages, M1 macrophages, fatty acid oxidation, JMJD3, epigenetic reprogramming, succinic acid, endotoxin tolerance, macrophage polarization
- MeSH terms
- Animals, Citric Acid Cycle, Fatty Acids, Glutamine, Glycolysis, Ketoglutaric Acids, Lipopolysaccharides, Macrophage Activation, Macrophages, Oxidation-Reduction, Oxidative Phosphorylation, Phenotype, NF-kappa B, Sequence Analysis, RNA, Succinic Acid, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, Epigenesis, Genetic, Chromatin Immunoprecipitation, Mice, Metabolomics, Cellular Reprogramming
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