Nucleophosmin 1 promotes mucosal immunity by supporting mitochondrial oxidative phosphorylation and ILC3 activity.

Journal

Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354

Informations de publication

Date de publication:
05 Aug 2024
Historique:
received: 12 06 2023
accepted: 10 07 2024
medline: 6 8 2024
pubmed: 6 8 2024
entrez: 5 8 2024
Statut: aheadofprint

Résumé

Nucleophosmin 1 (NPM1) is commonly mutated in myelodysplastic syndrome (MDS) and acute myeloid leukemia. Concurrent inflammatory bowel diseases (IBD) and MDS are common, indicating a close relationship between IBD and MDS. Here we examined the function of NPM1 in IBD and colitis-associated colorectal cancer (CAC). NPM1 expression was reduced in patients with IBD. Npm1

Identifiants

DOI: 10.1038/s41590-024-01921-x PMID: 39103576
pubmed: 39103576
doi: 10.1038/s41590-024-01921-x
pii: 10.1038/s41590-024-01921-x
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024. The Author(s).

Références

Neurath, M. Current and emerging therapeutic targets for IBD. Nat. Rev. Gastroenterol. Hepatol. 14, 688 (2017).
pubmed: 29018274 doi: 10.1038/nrgastro.2017.138
Kobayashi, T. et al. Ulcerative colitis. Nat. Rev. Dis. Primers 6, 74 (2020).
pubmed: 32913180 doi: 10.1038/s41572-020-0205-x
Baumgart, D. C. & Sandborn, W. J. Crohn’s disease. Lancet 380, 1590–1605 (2012).
pubmed: 22914295 doi: 10.1016/S0140-6736(12)60026-9
Danese, S. & Fiocchi, C. Ulcerative colitis. N. Engl. J. Med. 365, 1713–1725 (2011).
pubmed: 22047562 doi: 10.1056/NEJMra1102942
Hibi, T. & Ogata, H. Novel pathophysiological concepts of inflammatory bowel disease. J. Gastroenterol. 41, 10–16 (2006).
pubmed: 16501852 doi: 10.1007/s00535-005-1744-3
Ogawa, S. Genetics of MDS. Blood 133, 1049–1059 (2019).
pubmed: 30670442 pmcid: 6587668 doi: 10.1182/blood-2018-10-844621
Bejar, R., Levine, R. & Ebert, B. L. Unraveling the molecular pathophysiology of myelodysplastic syndromes. J. Clin. Oncol. 29, 504–515 (2011).
pubmed: 21220588 pmcid: 3969457 doi: 10.1200/JCO.2010.31.1175
Tefferi, A. & Vardiman, J. W. Myelodysplastic syndromes. N. Engl. J. Med. 361, 1872–1885 (2009).
pubmed: 19890130 doi: 10.1056/NEJMra0902908
Kono, M. et al. Induction of complete remission by azacitidine in a patient with myelodysplastic syndrome-associated inflammatory bowel disease. J. Crohns Colitis 12, 499–502 (2018).
pubmed: 29253109 doi: 10.1093/ecco-jcc/jjx170
Hebbar, M. et al. Association between myelodysplastic syndromes and inflammatory bowel diseases. Report of seven new cases and review of the literature. Leukemia 11, 2188–2191 (1997).
pubmed: 9447839 doi: 10.1038/sj.leu.2400863
Harewood, G. C., Loftus, E. V. Jr., Tefferi, A., Tremaine, W. J. & Sandborn, W. J. Concurrent inflammatory bowel disease and myelodysplastic syndromes. Inflamm. Bowel Dis. 5, 98–103 (1999).
pubmed: 10338378 doi: 10.1097/00054725-199905000-00005
Wang, Z., Zhou, Y. & Liu, Y. Concurrent inflammatory bowel disease and myelodysplastic syndrome: report of nine new cases and a review of the literature. Dig. Dis. Sci. 53, 1929–1932 (2008).
pubmed: 18080760 doi: 10.1007/s10620-007-0090-0
Nakamura, F. et al. Simultaneous occurrence of inflammatory bowel disease and myelodysplastic syndrome due to chromosomal abnormalities in bone marrow cells. Digestion 79, 215–219 (2009).
pubmed: 19390193 doi: 10.1159/000213486
Kristinsson, S. Y. et al. Chronic immune stimulation might act as a trigger for the development of acute myeloid leukemia or myelodysplastic syndromes. J. Clin. Oncol. 29, 2897 (2011).
pubmed: 21690473 pmcid: 3138717 doi: 10.1200/JCO.2011.34.8540
Komrokji, R. S. et al. Autoimmune diseases and myelodysplastic syndromes. Am. J. Hematol. 91, E280–E283 (2016).
pubmed: 26875020 doi: 10.1002/ajh.24333
Khan, N. et al. Incidence of acute myeloid leukemia and myelodysplastic syndrome in patients with inflammatory bowel disease and the impact of thiopurines on their risk. Am. J. Gastroenterol. 116, 741–747 (2021).
pubmed: 33982944 doi: 10.14309/ajg.0000000000001058
Makishima, H. et al. Dynamics of clonal evolution in myelodysplastic syndromes. Nat. Genet. 49, 204–212 (2017).
pubmed: 27992414 doi: 10.1038/ng.3742
Hingorani, K., Szebeni, A. & Olson, M. O. Mapping the functional domains of nucleolar protein B23. J. Biol. Chem. 275, 24451–24457 (2000).
pubmed: 10829026 doi: 10.1074/jbc.M003278200
Uckelmann, H. J. et al. Mutant NPM1 directly regulates oncogenic transcription in acute myeloid leukemia. Cancer Discov. 13, 746–765 (2023).
pubmed: 36455613 pmcid: 10084473 doi: 10.1158/2159-8290.CD-22-0366
Wang, X. Q. D. et al. Mutant NPM1 hijacks transcriptional hub to maintain pathogenic gene programs in acute myeloid leukemia. Cancer Discov. 13, 724–745 (2023).
pubmed: 36455589 doi: 10.1158/2159-8290.CD-22-0424
Morganti, C. et al. NPM1 ablation induces HSC aging and inflammation to develop myelodysplastic syndrome exacerbated by p53 loss. EMBO Rep. 23, e54262 (2022).
pubmed: 35229971 pmcid: 9066051 doi: 10.15252/embr.202154262
Raval, A. et al. Effect of nucleophosmin 1 haploinsufficiency on hematopoietic stem cells. Leukemia 26, 853–855 (2012).
pubmed: 21979879 doi: 10.1038/leu.2011.270
Artis, D. & Spits, H. The biology of innate lymphoid cells. Nature 517, 293–301 (2015).
pubmed: 25592534 doi: 10.1038/nature14189
Eberl, G. et al. An essential function for the nuclear receptor RORγt in the generation of fetal lymphoid tissue inducer cells. Nat. Immunol. 5, 64–73 (2004).
pubmed: 14691482 doi: 10.1038/ni1022
Kiss, E. A. et al. Natural aryl hydrocarbon receptor ligands control organogenesis of intestinal lymphoid follicles. Science 334, 1561–1565 (2011).
pubmed: 22033518 doi: 10.1126/science.1214914
Qiu, J. et al. The aryl hydrocarbon receptor regulates gut immunity through modulation of innate lymphoid cells. Immunity 36, 92–104 (2012).
pubmed: 22177117 doi: 10.1016/j.immuni.2011.11.011
Guo, X. et al. Induction of innate lymphoid cell-derived interleukin-22 by the transcription factor STAT3 mediates protection against intestinal infection. Immunity 40, 25–39 (2014).
pubmed: 24412612 pmcid: 3919552 doi: 10.1016/j.immuni.2013.10.021
Sonnenberg, G. F. et al. Innate lymphoid cells promote anatomical containment of lymphoid-resident commensal bacteria. Science 336, 1321–1325 (2012).
pubmed: 22674331 pmcid: 3659421 doi: 10.1126/science.1222551
Huber, S. et al. IL-22BP is regulated by the inflammasome and modulates tumorigenesis in the intestine. Nature 491, 259–263 (2012).
pubmed: 23075849 pmcid: 3493690 doi: 10.1038/nature11535
Uzzan, M. et al. Ulcerative colitis is characterized by a plasmablast-skewed humoral response associated with disease activity. Nat. Med. 28, 766–779 (2022).
pubmed: 35190725 pmcid: 9107072 doi: 10.1038/s41591-022-01680-y
Schinke, C. et al. IL8-CXCR2 pathway inhibition as a therapeutic strategy against MDS and AML stem cells. Blood 125, 3144–3152 (2015).
pubmed: 25810490 pmcid: 4432009 doi: 10.1182/blood-2015-01-621631
Muto, T. et al. Concurrent loss of Ezh2 and Tet2 cooperates in the pathogenesis of myelodysplastic disorders. J. Exp. Med. 210, 2627–2639 (2013).
pubmed: 24218139 pmcid: 3832936 doi: 10.1084/jem.20131144
Gobert, A. P. et al. Protective role of spermidine in colitis and colon carcinogenesis. Gastroenterology 162, 813–827 (2022).
pubmed: 34767785 doi: 10.1053/j.gastro.2021.11.005
Shah, S. C. & Itzkowitz, S. H. Colorectal cancer in inflammatory bowel disease: mechanisms and management. Gastroenterology 162, 715–730 (2022).
pubmed: 34757143 doi: 10.1053/j.gastro.2021.10.035
Vu, T. et al. Serine-threonine kinase receptor-associated protein is a critical mediator of APC mutation-induced intestinal tumorigenesis through a feed-forward mechanism. Gastroenterology 162, 193–208 (2022).
pubmed: 34520730 doi: 10.1053/j.gastro.2021.09.010
Kuo, W. T. et al. The tight junction protein ZO-1 is dispensable for barrier function but critical for effective mucosal repair. Gastroenterology 161, 1924–1939 (2021).
pubmed: 34478742 doi: 10.1053/j.gastro.2021.08.047
Luoma, A. M. et al. Molecular pathways of colon inflammation induced by cancer immunotherapy. Cell 182, 655–671 (2020).
pubmed: 32603654 pmcid: 7415717 doi: 10.1016/j.cell.2020.06.001
Allan, D. S. et al. An in vitro model of innate lymphoid cell function and differentiation. Mucosal Immunol. 8, 340–351 (2015).
pubmed: 25138665 doi: 10.1038/mi.2014.71
Di Luccia, B., Gilfillan, S., Cella, M., Colonna, M. & Huang, S. C.-C. ILC3s integrate glycolysis and mitochondrial production of reactive oxygen species to fulfill activation demands. J. Exp. Med. 216, 2231–2241 (2019).
pubmed: 31296736 pmcid: 6781001 doi: 10.1084/jem.20180549
Xiong, L. et al. Nutrition impact on ILC3 maintenance and function centers on a cell-intrinsic CD71–iron axis. Nat. Immunol. 24, 1671–1684 (2023).
pubmed: 37709985 pmcid: 11256193 doi: 10.1038/s41590-023-01612-z
Chamoto, K. et al. Mitochondrial activation chemicals synergize with surface receptor PD-1 blockade for T cell-dependent antitumor activity. Proc. Natl Acad. Sci. USA 114, E761–E770 (2017).
pubmed: 28096382 pmcid: 5293087 doi: 10.1073/pnas.1620433114
Inak, G. et al. Defective metabolic programming impairs early neuronal morphogenesis in neural cultures and an organoid model of Leigh syndrome. Nat. Commun. 12, 1929 (2021).
pubmed: 33771987 pmcid: 7997884 doi: 10.1038/s41467-021-22117-z
Weinberg, S. E., Sena, L. A. & Chandel, N. S. Mitochondria in the regulation of innate and adaptive immunity. Immunity 42, 406–417 (2015).
pubmed: 25786173 pmcid: 4365295 doi: 10.1016/j.immuni.2015.02.002
Lin, J., Kato, M., Nagata, K. & Okuwaki, M. Efficient DNA binding of NF-κB requires the chaperone-like function of NPM1. Nucleic Acids Res. 45, 3707–3723 (2017).
pubmed: 28003476
Barshad, G., Marom, S., Cohen, T. & Mishmar, D. Mitochondrial DNA transcription and its regulation: an evolutionary perspective. Trends Genet. 34, 682–692 (2018).
pubmed: 29945721 doi: 10.1016/j.tig.2018.05.009
Wculek, S. K. et al. Oxidative phosphorylation selectively orchestrates tissue macrophage homeostasis. Immunity 56, 516-+ (2023).
pubmed: 36738738 doi: 10.1016/j.immuni.2023.01.011
Ekstrand, M. I. et al. Mitochondrial transcription factor A regulates mtDNA copy number in mammals. Hum. Mol. Genet. 13, 935–944 (2004).
pubmed: 15016765 doi: 10.1093/hmg/ddh109
Fu, Z. et al. Mitochondrial transcription factor A in RORγt
pubmed: 34294718 pmcid: 8298438 doi: 10.1038/s41467-021-24755-9
Lee, K. M. et al. MYC and MCL1 cooperatively promote chemotherapy-resistant breast cancer stem cells via regulation of mitochondrial oxidative phosphorylation. Cell Metab. 26, 633–647 (2017).
pubmed: 28978427 pmcid: 5650077 doi: 10.1016/j.cmet.2017.09.009
Li, Z. & Hann, S. R. Nucleophosmin is essential for c-Myc nucleolar localization and c-Myc-mediated rDNA transcription. Oncogene 32, 1988–1994 (2013).
pubmed: 22665062 doi: 10.1038/onc.2012.227
Scarpulla, R. C. Transcriptional paradigms in mammalian mitochondrial biogenesis and function. Physiol. Rev. 88, 611–638 (2008).
pubmed: 18391175 doi: 10.1152/physrev.00025.2007
Dhar, S. K., Xu, Y., Chen, Y. M. & Clair, D. K. S. Specificity protein 1-dependent p53-mediated suppression of human manganese superoxide dismutase gene expression. J. Biol. Chem. 281, 21698–21709 (2006).
pubmed: 16740634 doi: 10.1074/jbc.M601083200
Wang, H. et al. p53 contributes to cardiovascular diseases via mitochondria dysfunction: a new paradigm. Free Radic. Biol. Med. 208, 846–858 (2023).
pubmed: 37776918 doi: 10.1016/j.freeradbiomed.2023.09.036
Ånensen, N. et al. Correlation analysis of p53 protein isoforms with mutations and therapy response in acute myeloid leukemia. Oncogene 31, 1533–1545 (2012).
pubmed: 21860418 doi: 10.1038/onc.2011.348
Zhong, Z. Y. et al. New mitochondrial DNA synthesis enables NLRP3 inflammasome activation. Nature 560, 198–203 (2018).
pubmed: 30046112 pmcid: 6329306 doi: 10.1038/s41586-018-0372-z
Kondo, T. et al. Identification and characterization of nucleophosmin/B23/numatrin which binds the anti-oncogenic transcription factor IRF-1 and manifests oncogenic activity. Oncogene 15, 1275–1281 (1997).
pubmed: 9315094 doi: 10.1038/sj.onc.1201286
Ron-Harel, N. et al. Mitochondrial biogenesis and proteome remodeling promote one-carbon metabolism for T cell activation. Cell Metab. 24, 104–117 (2016).
pubmed: 27411012 pmcid: 5330619 doi: 10.1016/j.cmet.2016.06.007
Xiao, P. et al. Phosphatase Shp2 exacerbates intestinal inflammation by disrupting macrophage responsiveness to interleukin-10. J. Exp. Med. 216, 337–349 (2019).
pubmed: 30610104 pmcid: 6363431 doi: 10.1084/jem.20181198
Zhou, Y. et al. USF1/CD90 signaling in maintaining glioblastoma stem cells and tumor-associated macrophages adhesion. Neuro Oncol. 24, 1482–1493 (2022).
pubmed: 35287174 pmcid: 10167418 doi: 10.1093/neuonc/noac063
Hua, Y., Laserstein, P. & Helmstaedter, M. Large-volume en-bloc staining for electron microscopy-based connectomics. Nat. Commun. 6, 7923 (2015).
pubmed: 26235643 doi: 10.1038/ncomms8923

Auteurs

Rongchuan Zhao (R)

Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science, Suzhou, China.
School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Jiao Yang (J)

Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, China.
ORCID: 0000-0002-1553-5425

Yunjiao Zhai (Y)

Advanced Medical Research Institute, Shandong University, Jinan, China.

Hong Zhang (H)

Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science, Suzhou, China.

Yuanshuai Zhou (Y)

Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science, Suzhou, China.
School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Lei Hong (L)

Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science, Suzhou, China.
School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Detian Yuan (D)

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.

Ruilong Xia (R)

The First Rehabilitation Hospital of Shanghai, Brain and Spinal Cord Innovation Research Center, School of Medicine, Advanced Institute of Translational Medicine, Tongji University, Shanghai, China.

Yanxiang Liu (Y)

Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, China.

Jinlin Pan (J)

Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science, Suzhou, China.
School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Shaheryar Shafi (S)

Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science, Suzhou, China.
School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
ORCID: 0000-0002-1936-4838

Guohua Shi (G)

Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science, Suzhou, China.
School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Ruobing Zhang (R)

Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science, Suzhou, China.
School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Dingsan Luo (D)

Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science, Suzhou, China.

Jinyun Yuan (J)

Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science, Suzhou, China.

Dejing Pan (D)

CAM-SU Genomic Resource Center, Soochow University, Suzhou, China.

Changgeng Peng (C)

The First Rehabilitation Hospital of Shanghai, Brain and Spinal Cord Innovation Research Center, School of Medicine, Advanced Institute of Translational Medicine, Tongji University, Shanghai, China. changgeng.peng@tongji.edu.cn.
Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China. changgeng.peng@tongji.edu.cn.
ORCID: 0000-0002-6707-2717

Shiyang Li (S)

Advanced Medical Research Institute, Shandong University, Jinan, China. lishiyang@sdu.edu.cn.
ORCID: 0000-0003-1487-4991

Minxuan Sun (M)

Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science, Suzhou, China. minxuan.sun@sibet.ac.cn.
School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. minxuan.sun@sibet.ac.cn.
ORCID: 0000-0003-2033-6268

Classifications MeSH