Macrophage migration inhibitory factor is overproduced through EGR1 in TET2
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
03 02 2022
03 02 2022
Historique:
received:
22
03
2021
accepted:
06
01
2022
entrez:
4
2
2022
pubmed:
5
2
2022
medline:
25
3
2022
Statut:
epublish
Résumé
Somatic mutation in TET2 gene is one of the most common clonal genetic events detected in age-related clonal hematopoiesis as well as in chronic myelomonocytic leukemia (CMML). In addition to being a pre-malignant state, TET2 mutated clones are associated with an increased risk of death from cardiovascular disease, which could involve cytokine/chemokine overproduction by monocytic cells. Here, we show in mice and in human cells that, in the absence of any inflammatory challenge, TET2 downregulation promotes the production of MIF (macrophage migration inhibitory factor), a pivotal mediator of atherosclerotic lesion formation. In healthy monocytes, TET2 is recruited to MIF promoter and interacts with the transcription factor EGR1 and histone deacetylases. Disruption of these interactions as a consequence of TET2-decreased expression favors EGR1-driven transcription of MIF gene and its secretion. MIF favors monocytic differentiation of myeloid progenitors. These results designate MIF as a chronically overproduced chemokine and a potential therapeutic target in patients with clonal TET2 downregulation in myeloid cells.
Identifiants
pubmed: 35115654
doi: 10.1038/s42003-022-03057-w
pii: 10.1038/s42003-022-03057-w
pmc: PMC8814058
doi:
Substances chimiques
Cytokines
0
DNA-Binding Proteins
0
EGR1 protein, human
0
Early Growth Response Protein 1
0
Egr1 protein, mouse
0
Macrophage Migration-Inhibitory Factors
0
Dioxygenases
EC 1.13.11.-
TET2 protein, human
EC 1.13.11.-
Tet2 protein, mouse
EC 1.13.11.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
110Subventions
Organisme : Institut National Du Cancer (French National Cancer Institute)
ID : PRTK-16-122
Informations de copyright
© 2022. The Author(s).
Références
Ito, S. et al. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science 333, 1300–1303 (2011).
pubmed: 21778364
pmcid: 3495246
doi: 10.1126/science.1210597
Lu, F., Liu, Y., Jiang, L., Yamaguchi, S. & Zhang, Y. Role of Tet proteins in enhancer activity and telomere elongation. Genes Dev. 28, 2103–2119 (2014).
pubmed: 25223896
pmcid: 4180973
doi: 10.1101/gad.248005.114
Wu, X. & Zhang, Y. TET-mediated active DNA demethylation: Mechanism, function and beyond. Nat. Rev. Genet. 18, 517–534 (2017).
pubmed: 28555658
doi: 10.1038/nrg.2017.33
Costa, Y. et al. NANOG-dependent function of TET1 and TET2 in establishment of pluripotency. Nature 495, 370–374 (2013).
pubmed: 23395962
pmcid: 3606645
doi: 10.1038/nature11925
Lio, C. W. et al. Tet2 and Tet3 cooperate with B-lineage transcription factors to regulate DNA modification and chromatin accessibility. Elife 5, e18290 (2016).
de la Rica, L. et al. PU.1 target genes undergo Tet2-coupled demethylation and DNMT3b-mediated methylation in monocyte-to-osteoclast differentiation. Genome Biol. 14, R99 (2013).
pubmed: 24028770
pmcid: 4054781
doi: 10.1186/gb-2013-14-9-r99
Mendes, K. et al. The epigenetic pioneer EGR2 initiates DNA demethylation in differentiating monocytes at both stable and transient binding sites | Enhanced Reader. Nat. Commun. 12, 1556 (2021).
pubmed: 33692344
pmcid: 7946903
doi: 10.1038/s41467-021-21661-y
Rampal, R. et al. DNA hydroxymethylation profiling reveals that WT1 mutations result in loss of TET2 function in acute myeloid leukemia. Cell Rep. 9, 1841–1855 (2014).
pubmed: 25482556
pmcid: 4267494
doi: 10.1016/j.celrep.2014.11.004
Wang, Y. et al. WT1 recruits TET2 to regulate its target gene expression and suppress leukemia cell proliferation. Mol. Cell 57, 662–673 (2015).
pubmed: 25601757
pmcid: 4336627
doi: 10.1016/j.molcel.2014.12.023
Sun, Z. et al. EGR1 recruits TET1 to shape the brain methylome during development and upon neuronal activity. Nat. Commun. 10, 3892 (2019).
pubmed: 31467272
pmcid: 6715719
doi: 10.1038/s41467-019-11905-3
Williams, K. et al. TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity. Nature 473, 343–348 (2011).
pubmed: 21490601
pmcid: 3408592
doi: 10.1038/nature10066
Zhong, J. et al. TET1 modulates H4K16 acetylation by controlling auto-acetylation of hMOF to affect gene regulation and DNA repair function. Nucleic Acids Res. 45, 672–684 (2017).
pubmed: 27733505
doi: 10.1093/nar/gkw919
Zhang, Q. et al. Tet2 is required to resolve inflammation by recruiting Hdac2 to specifically repress IL-6. Nature 525, 389–393 (2015).
pubmed: 26287468
pmcid: 4697747
doi: 10.1038/nature15252
Vella, P. et al. Tet proteins connect the O-linked N-acetylglucosamine transferase Ogt to chromatin in embryonic stem cells. Mol. Cell 49, 645–656 (2013).
pubmed: 23352454
doi: 10.1016/j.molcel.2012.12.019
Chen, Q., Chen, Y., Bian, C., Fujiki, R. & Yu, X. TET2 promotes histone O-GlcNAcylation during gene transcription. Nature 493, 561–564 (2013).
pubmed: 23222540
doi: 10.1038/nature11742
Deplus, R. et al. TET2 and TET3 regulate GlcNAcylation and H3K4 methylation through OGT and SET1/COMPASS. EMBO J. 32, 645–655 (2013).
pubmed: 23353889
pmcid: 3590984
doi: 10.1038/emboj.2012.357
Delhommeau, F. et al. Mutation in TET2 in myeloid cancers. N. Engl. J. Med. 360, 2289–2301 (2009).
pubmed: 19474426
doi: 10.1056/NEJMoa0810069
Lio, C. W. J., Yuita, H. & Rao, A. Dysregulation of the TET family of epigenetic regulators in lymphoid and myeloid malignancies. Blood 134, 1487–1497 (2019).
pubmed: 31467060
pmcid: 6839946
doi: 10.1182/blood.2019791475
Coltro, G. et al. Clinical, molecular, and prognostic correlates of number, type, and functional localization of TET2 mutations in chronic myelomonocytic leukemia (CMML)—a study of 1084 patients. Leukemia 34, 1407–1421 (2020).
pubmed: 31836856
doi: 10.1038/s41375-019-0690-7
Quivoron, C. et al. TET2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis. Cancer Cell 20, 25–38 (2011).
pubmed: 21723201
doi: 10.1016/j.ccr.2011.06.003
Li, Z. et al. Deletion of Tet2 in mice leads to dysregulated hematopoietic stem cells and subsequent development of myeloid malignancies. Blood 118, 4509–4518 (2011).
pubmed: 21803851
pmcid: 3952630
doi: 10.1182/blood-2010-12-325241
Ko, M. et al. Ten-eleven-translocation 2 (TET2) negatively regulates homeostasis and differentiation of hematopoietic stem cells in mice. Proc. Natl Acad. Sci. USA 108, 14566–14571 (2011).
pubmed: 21873190
pmcid: 3167529
doi: 10.1073/pnas.1112317108
Moran-Crusio, K. et al. Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation. Cancer Cell 20, 11–24 (2011).
pubmed: 21723200
pmcid: 3194039
doi: 10.1016/j.ccr.2011.06.001
Hirsch, P. et al. Genetic hierarchy and temporal variegation in the clonal history of acute myeloid leukaemia. Nat. Commun. 7, 12475 (2016).
pubmed: 27534895
pmcid: 4992157
doi: 10.1038/ncomms12475
Makishima, H. et al. Dynamics of clonal evolution in myelodysplastic syndromes. Nat. Genet. 49, 204–212 (2017).
pubmed: 27992414
doi: 10.1038/ng.3742
Kunimoto, H. et al. Cooperative epigenetic remodeling by TET2 loss and NRAS mutation drives myeloid transformation and MEK inhibitor sensitivity. Cancer Cell 33, 44–59.e8 (2018).
pubmed: 29275866
doi: 10.1016/j.ccell.2017.11.012
Busque, L. et al. Recurrent somatic TET2 mutations in normal elderly individuals with clonal hematopoiesis. Nat. Genet. 44, 1179–1181 (2012).
pubmed: 23001125
pmcid: 3483435
doi: 10.1038/ng.2413
Mason, C. C. et al. Age-related mutations and chronic myelomonocytic leukemia. Leukemia 30, 906–913 (2016).
pubmed: 26648538
doi: 10.1038/leu.2015.337
Jaiswal, S. et al. Age-related clonal hematopoiesis associated with adverse outcomes. N. Engl. J. Med. 371, 2488–2498 (2014).
pubmed: 25426837
pmcid: 4306669
doi: 10.1056/NEJMoa1408617
Fuster, J. J. et al. Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice. Science 355, 842–847 (2017).
pubmed: 28104796
pmcid: 5542057
doi: 10.1126/science.aag1381
Wang, Y. et al. Tet2-mediated clonal hematopoiesis in nonconditioned mice accelerates age-associated cardiac dysfunction. JCI Insight 5, e135204 (2020).
pmcid: 7213793
doi: 10.1172/jci.insight.135204
Jaiswal, S. & Libby, P. Clonal haematopoiesis: connecting ageing and inflammation in cardiovascular disease. Nat. Rev. Cardiol. 17, 137–144 (2020).
pubmed: 31406340
doi: 10.1038/s41569-019-0247-5
Cull, A. H., Snetsinger, B., Buckstein, R., Wells, R. A. & Rauh, M. J. Tet2 restrains inflammatory gene expression in macrophages. Exp. Hematol. 55, 56–70.e13 (2017).
pubmed: 28826859
doi: 10.1016/j.exphem.2017.08.001
Bick, A. G. et al. Genetic interleukin 6 signaling deficiency attenuates cardiovascular risk in clonal hematopoiesis. Circulation 141, 124–131 (2020).
pubmed: 31707836
doi: 10.1161/CIRCULATIONAHA.119.044362
Sano, S. et al. Tet2-mediated clonal hematopoiesis accelerates heart failure through a mechanism involving the IL-1β/NLRP3 inflammasome. J. Am. Coll. Cardiol. 71, 875–886 (2018).
pubmed: 29471939
pmcid: 5828038
doi: 10.1016/j.jacc.2017.12.037
David, J. R. Delayed hypersensitivity in vitro: Its mediation by cell-free substances formed by lymphoid cell-antigen interaction. Proc. Natl Acad. Sci. USA 56, 72–77 (1966).
pubmed: 5229858
pmcid: 285677
doi: 10.1073/pnas.56.1.72
Bloom, B. R. & Bennett, B. Mechanism of a reaction in vitro associated with delayed-type hypersensitivity. Science 153, 80–82 (1966).
pubmed: 5938421
doi: 10.1126/science.153.3731.80
Calandra, T. & Roger, T. Macrophage migration inhibitory factor: A regulator of innate immunity. Nat. Rev. Immunol. 3, 791–800 (2003).
pubmed: 14502271
pmcid: 7097468
doi: 10.1038/nri1200
Calandra, T. et al. MIF as a glucocorticoid-induced modulator of cytokine production. Nature 377, 68–71 (1995).
pubmed: 7659164
doi: 10.1038/377068a0
Calandra, T. et al. Protection from septic shock by neutralization of macrophage migration inhibitory factor. Nat. Med. 6, 164–170 (2000).
pubmed: 10655104
doi: 10.1038/72262
Bernhagen, J. et al. MIF is a noncognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment. Nat. Med. 13, 587–596 (2007).
pubmed: 17435771
doi: 10.1038/nm1567
Tilstam, P. V., Qi, D., Leng, L., Young, L. & Bucala, R. MIF family cytokines in cardiovascular diseases and prospects for precision-based therapeutics. Expert Opin. Ther. Targets 21, 671–683 (2017).
pubmed: 28562118
pmcid: 6130320
doi: 10.1080/14728222.2017.1336227
Kang, I. & Bucala, R. The immunobiology of MIF: Function, genetics, and prospects for precision medicine. Nat. Rev. Rheumatol. 15, 427–437 (2019).
pubmed: 31197253
doi: 10.1038/s41584-019-0238-2
Burger-Kentischer, A. et al. Reduction of the aortic inflammatory response in spontaneous atherosclerosis by blockade of macrophage migration inhibitory factor (MIF). Atherosclerosis 184, 28–38 (2006).
pubmed: 15921687
doi: 10.1016/j.atherosclerosis.2005.03.028
Bozza, M. et al. Targeted disruption of migration inhibitory factor gene reveals its critical role in sepsis. J. Exp. Med. 189, 341–346 (1999).
pubmed: 9892616
pmcid: 2192995
doi: 10.1084/jem.189.2.341
Mitchell, R. A. et al. Macrophage migration inhibitory factor (MIF) sustains macrophage proinflammatory function by inhibiting p53: Regulatory role in the innate immune response. Proc. Natl Acad. Sci. USA 99, 345–350 (2002).
pubmed: 11756671
doi: 10.1073/pnas.012511599
Shin, M. S. et al. Macrophage migration inhibitory factor regulates U1 small nuclear RNP immune complex-mediated activation of the NLRP3 inflammasome. Arthritis Rheumatol. 71, 109–120 (2019).
pubmed: 30009530
doi: 10.1002/art.40672
Pronier, E. et al. Inhibition of TET2-mediated conversion of 5-methylcytosine to 5-hydroxymethylcytosine disturbs erythroid and granulomonocytic differentiation of human hematopoietic progenitors. Blood 118, 2551–2555 (2011).
pubmed: 21734233
pmcid: 3292425
doi: 10.1182/blood-2010-12-324707
Itzykson, R. et al. Clonal architecture of chronic myelomonocytic leukemias. Blood 121, 2186–2198 (2013).
pubmed: 23319568
doi: 10.1182/blood-2012-06-440347
Merlevede, J. et al. Mutation allele burden remains unchanged in chronic myelomonocytic leukaemia responding to hypomethylating agents. Nat. Commun. 7, 10767 (2016).
pubmed: 26908133
pmcid: 4770084
doi: 10.1038/ncomms10767
Roger, T., Ding, X., Chanson, A. L., Renner, P. & Calandra, T. Regulation of constitutive and microbial pathogen-induced human macrophage migration inhibitory factor (MIF) gene expression. Eur. J. Immunol. 37, 3509–3521 (2007).
pubmed: 18034423
doi: 10.1002/eji.200737357
Roger, T., David, J., Glauser, M. P. & Calandra, T. MIF regulates innate immune responses through modulation of Toll-like receptor 4. Nature 414, 920–924 (2001).
pubmed: 11780066
doi: 10.1038/414920a
Lv, L. et al. Vpr targets TET2 for degradation by CRL4 VprBP E3 ligase to sustain IL-6 expression and enhance HIV-1 replication. Mol. Cell 70, 961–970.e5 (2018).
pubmed: 29883611
pmcid: 6071318
doi: 10.1016/j.molcel.2018.05.007
Carrillo-Jimenez, A. et al. TET2 regulates the neuroinflammatory response in microglia. Cell Rep. 29, 697–713.e8 (2019).
pubmed: 31618637
doi: 10.1016/j.celrep.2019.09.013
Itoh, H. et al. TET2-dependent IL-6 induction mediated by the tumor microenvironment promotes tumor metastasis in osteosarcoma. Oncogene 37, 2903–2920 (2018).
pubmed: 29515232
doi: 10.1038/s41388-018-0160-0
Lugrin, J. et al. Histone deacetylase inhibitors repress macrophage migration inhibitory factor (MIF) expression by targeting MIF gene transcription through a local chromatin deacetylation. Biochim. Biophys. Acta - Mol. Cell Res. 1793, 1749–1758 (2009).
doi: 10.1016/j.bbamcr.2009.09.007
Ko, M. et al. Modulation of TET2 expression and 5-methylcytosine oxidation by the CXXC domain protein IDAX. Nature 497, 122–126 (2013).
pubmed: 23563267
pmcid: 3643997
doi: 10.1038/nature12052
Li, X. et al. Ten-eleven translocation 2 interacts with forkhead box O3 and regulates adult neurogenesis. Nat. Commun. 8, 15903 (2017).
pubmed: 28660881
pmcid: 5493768
doi: 10.1038/ncomms15903
Reynaud, D. et al. IL-6 controls leukemic multipotent progenitor cell fate and contributes to chronic myelogenous leukemia development. Cancer Cell 20, 661–673 (2011).
pubmed: 22094259
pmcid: 3220886
doi: 10.1016/j.ccr.2011.10.012
Welner, R. S. et al. Treatment of chronic myelogenous leukemia by blocking cytokine alterations found in normal stem and progenitor cells. Cancer Cell 27, 671–681 (2015).
pubmed: 25965572
pmcid: 4447336
doi: 10.1016/j.ccell.2015.04.004
Harris, J., VanPatten, S., Deen, N. S., Al-Abed, Y. & Morand, E. F. Rediscovering MIF: New tricks for an old cytokine. Trends Immunol. 40, 447–462 (2019).
pubmed: 30962001
doi: 10.1016/j.it.2019.03.002
Hyrenius-Wittsten, A. et al. De novo activating mutations drive clonal evolution and enhance clonal fitness in KMT2A-rearranged leukemia. Nat. Commun. 9, 1770 (2018).
pubmed: 29720585
pmcid: 5932012
doi: 10.1038/s41467-018-04180-1
Morand, E. F., Leech, M. & Bernhagen, J. MIF: A new cytokine link between rheumatoid arthritis and atherosclerosis. Nat. Rev. Drug Discov. 5, 399–410 (2006).
pubmed: 16628200
doi: 10.1038/nrd2029
Sinitski, D. et al. Macrophage migration inhibitory factor (MIF)-based therapeutic concepts in atherosclerosis and inflammation. Thromb. Haemost. 119, 553–566 (2019).
pubmed: 30716779
doi: 10.1055/s-0039-1677803
Jaiswal, S. et al. Clonal Hematopoiesis and risk of atherosclerotic cardiovascular disease. N. Engl. J. Med. 377, 111–121 (2017).
pubmed: 28636844
pmcid: 6717509
doi: 10.1056/NEJMoa1701719
Illescas, O., Gomez-Verjan, J. C., García-Velázquez, L., Govezensky, T. & Rodriguez-Sosa, M. Macrophage migration inhibitory factor -173 G/C polymorphism: A global meta-analysis across the disease spectrum. Front. Genet. 9, 55 (2018).
pubmed: 29545822
pmcid: 5839154
doi: 10.3389/fgene.2018.00055
Kerschbaumer, R. J. et al. Neutralization of macrophage migration inhibitory factor (MIF) by fully human antibodies correlates with their specificity for the β-sheet structure of MIF. J. Biol. Chem. https://doi.org/10.1074/jbc.M111.329664 (2012).
Mahalingam, D. et al. Phase I study of imalumab (BAX69), a fully human recombinant antioxidized macrophage migration inhibitory factor antibody in advanced solid tumours. Br. J. Clin. Pharmacol. 86, 1836–1848 (2020).
doi: 10.1111/bcp.14289
Arber, D. A. et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 127, 2391–2405 (2016).
pubmed: 27069254
doi: 10.1182/blood-2016-03-643544
Newman, A. M. et al. Robust enumeration of cell subsets from tissue expression profiles. Nat. Methods 12, 453–457 (2015).
pubmed: 25822800
pmcid: 4739640
doi: 10.1038/nmeth.3337
Bencheikh, L. et al. Dynamic gene regulation by nuclear colony-stimulating factor 1 receptor in human monocytes and macrophages. Nat. Commun. 10, 1935 (2019).
pubmed: 31028249
pmcid: 6486619
doi: 10.1038/s41467-019-09970-9