RXRs control serous macrophage neonatal expansion and identity and contribute to ovarian cancer progression.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
03 04 2020
03 04 2020
Historique:
received:
26
09
2019
accepted:
28
02
2020
entrez:
5
4
2020
pubmed:
5
4
2020
medline:
24
7
2020
Statut:
epublish
Résumé
Tissue-resident macrophages (TRMs) populate all tissues and play key roles in homeostasis, immunity and repair. TRMs express a molecular program that is mostly shaped by tissue cues. However, TRM identity and the mechanisms that maintain TRMs in tissues remain poorly understood. We recently found that serous-cavity TRMs (LPMs) are highly enriched in RXR transcripts and RXR-response elements. Here, we show that RXRs control mouse serous-macrophage identity by regulating chromatin accessibility and the transcriptional regulation of canonical macrophage genes. RXR deficiency impairs neonatal expansion of the LPM pool and reduces the survival of adult LPMs through excess lipid accumulation. We also find that peritoneal LPMs infiltrate early ovarian tumours and that RXR deletion diminishes LPM accumulation in tumours and strongly reduces ovarian tumour progression in mice. Our study reveals that RXR signalling controls the maintenance of the serous macrophage pool and that targeting peritoneal LPMs may improve ovarian cancer outcomes.
Identifiants
pubmed: 32246014
doi: 10.1038/s41467-020-15371-0
pii: 10.1038/s41467-020-15371-0
pmc: PMC7125161
doi:
Substances chimiques
Retinoid X Receptors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1655Subventions
Organisme : NCI NIH HHS
ID : R01 CA190400
Pays : United States
Références
Bonnardel, J. & Guilliams, M. Developmental control of macrophage function. Curr. Opin. Immunol. 50, 64–74 (2018).
doi: 10.1016/j.coi.2017.12.001
Lavin, Y., Mortha, A., Rahman, A. & Merad, M. Regulation of macrophage development and function in peripheral tissues. Nat. Rev. Immunol. 15, 731–744 (2015).
doi: 10.1038/nri3920
pubmed: 4706379
pmcid: 4706379
Davies, L. C. et al. Distinct bone marrow-derived and tissue-resident macrophage lineages proliferate at key stages during inflammation. Nat. Commun. 4, 1886 (2013).
doi: 10.1038/ncomms2877
Mass E., et al. Specification of tissue-resident macrophages during organogenesis. Science 353, 1–10 (2016).
doi: 10.1126/science.aaf4238
AG, N. et al. The nuclear receptor LXRalpha controls the functional specialization of splenic macrophages. Nat. Immunol. 14, 831–839 (2013).
doi: 10.1038/ni.2622
Gautier, E. L. et al. Systemic analysis of PPARgamma in mouse macrophage populations reveals marked diversity in expression with critical roles in resolution of inflammation and airway immunity. J. Immunol. 189, 2614–2624 (2012).
doi: 10.4049/jimmunol.1200495
pubmed: 3537497
pmcid: 3537497
Kohyama, M. et al. Role for Spi-C in the development of red pulp macrophages and splenic iron homeostasis. Nature 457, 318–321 (2009).
doi: 10.1038/nature07472
Bain, C. C. & Jenkins, S. J. The biology of serous cavity macrophages. Cell Immunol. 330, 126–135 (2018).
doi: 10.1016/j.cellimm.2018.01.003
Ghosn, E. E. et al. Two physically, functionally, and developmentally distinct peritoneal macrophage subsets. Proc. Natl Acad. Sci. USA 107, 2568–2573 (2010).
doi: 10.1073/pnas.0915000107
Roberts, A. W. et al. Tissue-resident macrophages are locally programmed for silent clearance of apoptotic cells. Immunity 47, 913–27 e916 (2017).
doi: 10.1016/j.immuni.2017.10.006
pubmed: 5728676
pmcid: 5728676
Okabe, Y. & Medzhitov, R. Tissue-specific signals control reversible program of localization and functional polarization of macrophages. Cell 157, 832–844 (2014).
doi: 10.1016/j.cell.2014.04.016
pubmed: 4137874
pmcid: 4137874
Takenaka, E., Van, Vo. A., Yamashita-Kanemaru, Y., Shibuya, A. & Shibuya, K. Selective DNAM-1 expression on small peritoneal macrophages contributes to CD4(+) T cell costimulation. Sci. Rep. 8, 15180 (2018).
doi: 10.1038/s41598-018-33437-4
pubmed: 6185969
pmcid: 6185969
Hashimoto, D. et al. Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes. Immunity 38, 792–804 (2013).
doi: 10.1016/j.immuni.2013.04.004
Yona, S. et al. Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Immunity 38, 79–91 (2013).
doi: 10.1016/j.immuni.2012.12.001
Sheng, J., Ruedl, C. & Karjalainen, K. Most tissue-resident macrophages except microglia are derived from fetal hematopoietic stem cells. Immunity 43, 382–393 (2015).
doi: 10.1016/j.immuni.2015.07.016
Bain, C. C. et al. Long-lived self-renewing bone marrow-derived macrophages displace embryo-derived cells to inhabit adult serous cavities. Nat. Commun. 7, ncomms11852 (2016).
doi: 10.1038/ncomms11852
pubmed: 4910019
pmcid: 4910019
Liu, Z. et al. Fate mapping via Ms4a3-expression history traces monocyte-derived cells. Cell 178, 1509–25 e1519 (2019).
doi: 10.1016/j.cell.2019.08.009
Rosas, M. et al. The transcription factor Gata6 links tissue macrophage phenotype and proliferative renewal. Science 344, 645–648 (2014).
doi: 10.1126/science.1251414
pubmed: 4185421
pmcid: 4185421
Gautier, E. L. et al. Gata6 regulates aspartoacylase expression in resident peritoneal macrophages and controls their survival. J. Exp. Med. 211, 1525–1531 (2014).
doi: 10.1084/jem.20140570
pubmed: 4113942
pmcid: 4113942
Kim, K. W. et al. MHC II+ resident peritoneal and pleural macrophages rely on IRF4 for development from circulating monocytes. J. Exp. Med. 213, 1951–1959 (2016).
doi: 10.1084/jem.20160486
pubmed: 5030807
pmcid: 5030807
Dawson, M. I. & Xia, Z. The retinoid X receptors and their ligands. Biochim Biophysic Acta 1821, 21–56 (2012).
doi: 10.1016/j.bbalip.2011.09.014
Rőszer, T., Menendez-Gutierrez, M. P., Cedenilla, M., Ricote, M. & Retinoid, X receptors in macrophage biology. Trends Endocrinol. Metab. 460–468 (2013).
Lefebvre, P., Benomar, Y. & Staels, B. Retinoid X receptors: common heterodimerization partners with distinct functions. Trends Endocrinol. Metab. 21, 676–683 (2010).
doi: 10.1016/j.tem.2010.06.009
Nunez, V. et al. Retinoid X receptor alpha controls innate inflammatory responses through the up-regulation of chemokine expression. Proc. Natl Acad. Sci. USA 107, 10626–10631 (2010).
doi: 10.1073/pnas.0913545107
Menendez-Gutierrez, M. P. et al. Retinoid X receptors orchestrate osteoclast differentiation and postnatal bone remodeling. J. Clin. Invest. 125, 809–823 (2015).
doi: 10.1172/JCI77186
pubmed: 4319420
pmcid: 4319420
Rőszer, T. et al. Autoimmune kidney disease and impaired engulfment of apoptotic cells in mice with macrophage peroxisome proliferator-activated receptor gamma or retinoid X receptor alpha deficiency. J. Immunol. 186, 621–631 (2011).
doi: 10.4049/jimmunol.1002230
Lavin, Y. et al. Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment. Cell 159, 1312–1326 (2014).
doi: 10.1016/j.cell.2014.11.018
pubmed: 4437213
pmcid: 4437213
Ricote, M. et al. Normal hematopoiesis after conditional targeting of RXRalpha in murine hematopoietic stem/progenitor cells. J. Leukoc. Biol. 80, 850–861 (2006).
doi: 10.1189/jlb.0206097
Gosselin, D. et al. Environment drives selection and function of enhancers controlling tissue-specific macrophage identities. Cell 159, 1327–1340 (2014).
doi: 10.1016/j.cell.2014.11.023
pubmed: 4364385
pmcid: 4364385
Buechler, M. B. et al. A stromal niche defined by expression of the transcription factor WT1 mediates programming and homeostasis of cavity-resident macrophages. Immunity 51, 119–30 e115 (2019).
doi: 10.1016/j.immuni.2019.05.010
Cassado Ados, A. et al. Cellular renewal and improvement of local cell effector activity in peritoneal cavity in response to infectious stimuli. PLoS One 6, e22141 (2011).
doi: 10.1371/journal.pone.0022141
Toyonaga, K. et al. C-Type lectin receptor DCAR recognizes mycobacterial phosphatidyl-inositol mannosides to promote a Th1 response during infection. Immunity 45, 1245–1257 (2016).
doi: 10.1016/j.immuni.2016.10.012
Cain, D. W. et al. Identification of a tissue-specific, C/EBPbeta-dependent pathway of differentiation for murine peritoneal macrophages. J. Immunol. 191, 4665–4675 (2013).
doi: 10.4049/jimmunol.1300581
Evans, R. M. & Mangelsdorf, D. J. Nuclear receptors, RXR, and the big bang. Cell 157, 255–266 (2014).
doi: 10.1016/j.cell.2014.03.012
pubmed: 4029515
pmcid: 4029515
Liu F., Wu D., Wang X. Roles of CTCF in conformation and functions of chromosome. Semin. Cell Dev. Biol. 168–173 (2018).
Kim, S., Yu, N. K. & Kaang, B. K. CTCF as a multifunctional protein in genome regulation and gene expression. Exp. Mol. Med. 47, e166 (2015).
doi: 10.1038/emm.2015.33
pubmed: 4491725
pmcid: 4491725
Hoeffel, G. et al. C-Myb(+) erythro-myeloid progenitor-derived fetal monocytes give rise to adult tissue-resident macrophages. Immunity 42, 665–678 (2015).
doi: 10.1016/j.immuni.2015.03.011
pubmed: 4545768
pmcid: 4545768
de Boer, J. et al. Transgenic mice with hematopoietic and lymphoid specific expression of Cre. Eur. J. Immunol. 33, 314–325 (2003).
doi: 10.1002/immu.200310005
pubmed: 12548562
pmcid: 12548562
Davies, L. C. et al. A quantifiable proliferative burst of tissue macrophages restores homeostatic macrophage populations after acute inflammation. Eur. J. Immunol. 41, 2155–2164 (2011).
doi: 10.1002/eji.201141817
pubmed: 21710478
pmcid: 21710478
Lu, N., Shen, Q., Mahoney, T. R., Liu, X. & Zhou, Z. Three sorting nexins drive the degradation of apoptotic cells in response to PtdIns(3)P signaling. Mol. Biol. Cell 22, 354–374 (2011).
doi: 10.1091/mbc.e10-09-0756
pubmed: 3031466
pmcid: 3031466
Longatti, A. et al. TBC1D14 regulates autophagosome formation via Rab11- and ULK1-positive recycling endosomes. J. Cell Biol. 197, 659–675 (2012).
doi: 10.1083/jcb.201111079
pubmed: 3365497
pmcid: 3365497
Xu, X. et al. Obesity activates a program of lysosomal-dependent lipid metabolism in adipose tissue macrophages independently of classic activation. Cell Metab. 18, 816–830 (2013).
doi: 10.1016/j.cmet.2013.11.001
pubmed: 3939841
pmcid: 3939841
Saraswathi, V. & Hasty, A. H. Inhibition of long-chain acyl coenzyme A synthetases during fatty acid loading induces lipotoxicity in macrophages. Arterioscler. Thromb. Vasc. Biol. 29, 1937–1943 (2009).
doi: 10.1161/ATVBAHA.109.195362
pubmed: 2766024
pmcid: 2766024
Tabas, I. & Bornfeldt, K. E. Macrophage phenotype and function in different stages of atherosclerosis. Circ. Res. 118, 653–667 (2016).
doi: 10.1161/CIRCRESAHA.115.306256
pubmed: 4762068
pmcid: 4762068
Torre, L. A. et al. Ovarian cancer statistics, 2018. CA Cancer J. Clin. 68, 284–296 (2018).
doi: 10.3322/caac.21456
pubmed: 6621554
pmcid: 6621554
Dizon, D. S. et al. Clinical cancer advances 2016: annual report on progress against cancer from the american society of clinical oncology. J. Clin. Oncol. 34, 987–1011 (2016).
doi: 10.1200/JCO.2015.65.8427
pubmed: 5075244
pmcid: 5075244
Wang, J. & Kubes, P. A reservoir of mature cavity macrophages that can rapidly invade visceral organs to affect tissue repair. Cell 165, 668–678 (2016).
doi: 10.1016/j.cell.2016.03.009
Scarlett, U. K. et al. Ovarian cancer progression is controlled by phenotypic changes in dendritic cells. J. Exp. Med. 209, 495–506 (2012).
doi: 10.1084/jem.20111413
pubmed: 3302234
pmcid: 3302234
Heng, T. S. & Painter, M. W. Immunological Genome Project C. The Immunological Genome Project: networks of gene expression in immune cells. Nat. Immunol. 9, 1091–1094 (2008).
doi: 10.1038/ni1008-1091
Louis, C. et al. Specific contributions of CSF-1 and GM-CSF to the dynamics of the mononuclear phagocyte system. J. Immunol. 195, 134–144 (2015).
doi: 10.4049/jimmunol.1500369
MacDonald, K. P. et al. An antibody against the colony-stimulating factor 1 receptor depletes the resident subset of monocytes and tissue- and tumor-associated macrophages but does not inhibit inflammation. Blood 116, 3955–3963 (2010).
doi: 10.1182/blood-2010-02-266296
Cecchini, M. G. et al. Role of colony stimulating factor-1 in the establishment and regulation of tissue macrophages during postnatal development of the mouse. Development 120, 1357–1372 (1994).
Ryan, G. R. et al. Rescue of the colony-stimulating factor 1 (CSF-1)-nullizygous mouse (Csf1(op)/Csf1(op)) phenotype with a CSF-1 transgene and identification of sites of local CSF-1 synthesis. Blood 98, 74–84 (2001).
doi: 10.1182/blood.V98.1.74
Dai, X. M., Zong, X. H., Sylvestre, V. & Stanley, E. R. Incomplete restoration of colony-stimulating factor 1 (CSF-1) function in CSF-1-deficient Csf1op/Csf1op mice by transgenic expression of cell surface CSF-1. Blood 103, 1114–1123 (2004).
doi: 10.1182/blood-2003-08-2739
Wong, K. et al. Phosphatidylserine receptor Tim-4 is essential for the maintenance of the homeostatic state of resident peritoneal macrophages. Proc. Natl Acad. Sci. USA 107, 8712–8717 (2010).
doi: 10.1073/pnas.0910929107
Settembre, C. & Ballabio, A. Lysosome: regulator of lipid degradation pathways. Trends Cell Biol. 24, 743–750 (2014).
doi: 10.1016/j.tcb.2014.06.006
pubmed: 4247383
pmcid: 4247383
Zhou, Z. & Yu, X. Phagosome maturation during the removal of apoptotic cells: receptors lead the way. Trends Cell Biol. 18, 474–485 (2008).
doi: 10.1016/j.tcb.2008.08.002
pubmed: 3125982
pmcid: 3125982
Markman, M. Poly (ADP-ribose) polymerase inhibitors in the management of ovarian cancer. Women’s Health 14, 1–6 (2018).
Weiss, J. M. et al. Itaconic acid mediates crosstalk between macrophage metabolism and peritoneal tumors. J. Clin. Investig. 128, 3794–3805 (2018).
doi: 10.1172/JCI99169
Finkernagel, F. et al. The transcriptional signature of human ovarian carcinoma macrophages is associated with extracellular matrix reorganization. Oncotarget 7, 75339–75352 (2016).
doi: 10.18632/oncotarget.12180
pubmed: 5342745
pmcid: 5342745
Li, M. et al. Retinoid X receptor ablation in adult mouse keratinocytes generates an atopic dermatitis triggered by thymic stromal lymphopoietin. Proc. Natl Acad. Sci. USA 102, 14795–14800 (2005).
doi: 10.1073/pnas.0507385102
Srinivas, S. et al. Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus. BMC Dev. Biol. 1, 4 (2001).
doi: 10.1186/1471-213X-1-4
pubmed: 31338
pmcid: 31338
Jimenez-Carretero, D., Ligos, J. M., Martinez-Lopez, M., Sancho, D. & Montoya, M. C. Flow cytometry data preparation guidelines for improved automated phenotypic analysis. J. Immunol. 200, 3319–3331 (2018).
doi: 10.4049/jimmunol.1800446
Buenrostro, J. D., Giresi, P. G., Zaba, L. C., Chang, H. Y. & Greenleaf, W. J. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat. Methods 10, 1213–1218 (2013).
doi: 10.1038/nmeth.2688
pubmed: 3959825
pmcid: 3959825
Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357–359 (2012).
doi: 10.1038/nmeth.1923
pubmed: 3322381
pmcid: 3322381
Zhang, Y. et al. Model-based analysis of ChIP-Seq (MACS). Genome Biol. 9, R137 (2008).
doi: 10.1186/gb-2008-9-9-r137
pubmed: 2592715
pmcid: 2592715
Robinson, M. D., McCarthy, D. J. & Smyth, G. K. edgeR: A bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139–140 (2010).
doi: 10.1093/bioinformatics/btp616
Heinz, S. et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol. Cell 38, 576–589 (2010).
doi: 10.1016/j.molcel.2010.05.004
pubmed: 2898526
pmcid: 2898526