Rapid unleashing of macrophage efferocytic capacity via transcriptional pause release.


Journal

Nature
ISSN: 1476-4687
Titre abrégé: Nature
Pays: England
ID NLM: 0410462

Informations de publication

Date de publication:
13 Mar 2024
Historique:
received: 27 06 2023
accepted: 07 02 2024
medline: 14 3 2024
pubmed: 14 3 2024
entrez: 14 3 2024
Statut: aheadofprint

Résumé

During development, inflammation or tissue injury, macrophages may successively engulf and process multiple apoptotic corpses via efferocytosis to achieve tissue homeostasis

Identifiants

pubmed: 38480883
doi: 10.1038/s41586-024-07172-y
pii: 10.1038/s41586-024-07172-y
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024. The Author(s), under exclusive licence to Springer Nature Limited.

Références

Morioka, S., Maueröder, C. & Ravichandran, K. S. Living on the edge: efferocytosis at the interface of homeostasis and pathology. Immunity 50, 1149–1162 (2019).
pubmed: 31117011 pmcid: 6721617 doi: 10.1016/j.immuni.2019.04.018
Muse, G. W. et al. RNA polymerase is poised for activation across the genome. Nat. Genet. 39, 1507–1511 (2007).
pubmed: 17994021 pmcid: 2365887 doi: 10.1038/ng.2007.21
Chawla, A. et al. A PPARy-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis. Mol. Cell 7, 161–171 (2001).
pubmed: 11172721 doi: 10.1016/S1097-2765(01)00164-2
Czimmerer, Z. & Nagy, L. Epigenomic regulation of macrophage polarization: where do the nuclear receptors belong? Immunol. Rev. 317, 152–165 (2023).
pubmed: 37074820 doi: 10.1111/imr.13209
Boada-Romero, E., Martinez, J., Heckmann, B. L. & Green, D. R. The clearance of dead cells by efferocytosis. Nat. Rev. Mol. Cell Biol. 21, 398–414 (2020).
pubmed: 32251387 pmcid: 7392086 doi: 10.1038/s41580-020-0232-1
Morioka, S. et al. Chimeric efferocytic receptors improve apoptotic cell clearance and alleviate inflammation. Cell 185, 4887–4903.e4817 (2022).
pubmed: 36563662 pmcid: 9930200 doi: 10.1016/j.cell.2022.11.029
Yurdagul, A. et al. Macrophage metabolism of apoptotic cell-derived arginine promotes continual efferocytosis and resolution of injury. Cell Metab. 31, 518–533.e510 (2020).
pubmed: 32004476 pmcid: 7173557 doi: 10.1016/j.cmet.2020.01.001
Core, L. J., Waterfall, J. J. & Lis, J. T. Nascent RNA sequencing reveals widespread pausing and divergent initiation at human promoters. Science 322, 1845–1848 (2008).
pubmed: 19056941 pmcid: 2833333 doi: 10.1126/science.1162228
Gressel, S., Schwalb, B. & Cramer, P. The pause-initiation limit restricts transcription activation in human cells. Nat. Commun. 10, 3603 (2019).
pubmed: 31399571 pmcid: 6689055 doi: 10.1038/s41467-019-11536-8
Shao, W. & Zeitlinger, J. Paused RNA polymerase II inhibits new transcriptional initiation. Nat. Genet. 49, 1045–1051 (2017).
pubmed: 28504701 doi: 10.1038/ng.3867
Abuhashem, A., Garg, V. & Hadjantonakis, A.-K. RNA polymerase II pausing in development: orchestrating transcription. Open Biol. 12, 210220 (2022).
pubmed: 34982944 pmcid: 8727152 doi: 10.1098/rsob.210220
Yu, L. et al. Negative elongation factor complex enables macrophage inflammatory responses by controlling anti-inflammatory gene expression. Nat. Commun. 11, 2286 (2020).
pubmed: 32385332 pmcid: 7210294 doi: 10.1038/s41467-020-16209-5
Yamaguchi, Y., Inukai, N., Narita, T., Wada, T. & Handa, H. Evidence that negative elongation factor represses transcription elongation through binding to a DRB sensitivity-inducing factor/RNA polymerase II complex and RNA. Mol. Cell. Biol. 22, 2918–2927 (2002).
pubmed: 11940650 pmcid: 133766 doi: 10.1128/MCB.22.9.2918-2927.2002
Wei, P., Garber, M. E., Fang, S. M., Fischer, W. H. & Jones, K. A. A novel CDK9-associated C-type cyclin interacts directly with HIV-1 Tat and mediates its high-affinity, loop-specific binding to TAR RNA. Cell 92, 451–462 (1998).
pubmed: 9491887 doi: 10.1016/S0092-8674(00)80939-3
Fujinaga, K. et al. Dynamics of human immunodeficiency virus transcription: P-TEFb phosphorylates RD and dissociates negative effectors from the transactivation response element. Mol. Cell. Biol. 24, 787–795 (2004).
pubmed: 14701750 pmcid: 343783 doi: 10.1128/MCB.24.2.787-795.2004
Kim, J. B. & Sharp, P. A. Positive transcription elongation factor B phosphorylates hSPT5 and RNA polymerase II carboxyl-terminal domain independently of cyclin-dependent kinase-activating kinase. J. Biol. Chem. 276, 12317–12323 (2001).
pubmed: 11145967 doi: 10.1074/jbc.M010908200
Henriques, T. et al. Stable pausing by RNA polymerase II provides an opportunity to target and integrate regulatory signals. Mol. Cell 52, 517–528 (2013).
pubmed: 24184211 doi: 10.1016/j.molcel.2013.10.001
Buckley, M. S., Kwak, H., Zipfel, W. R. & Lis, J. T. Kinetics of promoter Pol II on Hsp70 reveal stable pausing and key insights into its regulation. Genes Dev. 28, 14–19 (2014).
pubmed: 24395245 pmcid: 3894409 doi: 10.1101/gad.231886.113
Lavin, Y. et al. Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment. Cell 159, 1312–1326 (2014).
pubmed: 25480296 pmcid: 4437213 doi: 10.1016/j.cell.2014.11.018
Boettiger, A. N. & Levine, M. Synchronous and stochastic patterns of gene activation in the Drosophila embryo. Science 325, 471–473 (2009).
pubmed: 19628867 pmcid: 4280267 doi: 10.1126/science.1173976
Saha, R. N. et al. Rapid activity-induced transcription of Arc and other IEGs relies on poised RNA polymerase II. Nat. Neurosci. 14, 848–856 (2011).
pubmed: 21623364 pmcid: 3125443 doi: 10.1038/nn.2839
Rougvie, A. E. & Lis, J. T. The RNA polymerase II molecule at the 5’ end of the uninduced hsp70 gene of D. melanogaster is transcriptionally engaged. Cell 54, 795–804 (1988).
pubmed: 3136931 doi: 10.1016/S0092-8674(88)91087-2
Mahat, D. B., Salamanca, H. H., Duarte, F. M., Danko, C. G. & Lis, J. T. Mammalian heat shock response and mechanisms underlying its genome-wide transcriptional regulation. Mol. Cell 62, 63–78 (2016).
pubmed: 27052732 pmcid: 4826300 doi: 10.1016/j.molcel.2016.02.025
Kwak, H., Fuda, N. J., Core, L. J. & Lis, J. T. Precise maps of RNA polymerase reveal how promoters direct initiation and pausing. Science 339, 950–953 (2013).
pubmed: 23430654 pmcid: 3974810 doi: 10.1126/science.1229386
Lücking, U. et al. Identification of atuveciclib (BAY 1143572), the first highly selective, clinical PTEFb/CDK9 inhibitor for the treatment of cancer. ChemMedChem 12, 1776–1793 (2017).
pubmed: 28961375 pmcid: 5698704 doi: 10.1002/cmdc.201700447
Jonkers, I., Kwak, H. & Lis, J. T. Genome-wide dynamics of Pol II elongation and its interplay with promoter proximal pausing, chromatin, and exons. eLife 3, e02407 (2014).
pubmed: 24843027 pmcid: 4001325 doi: 10.7554/eLife.02407
Liang, K. et al. Targeting processive transcription elongation via SEC disruption for MYC-induced cancer therapy. Cell 175, 766–779.e717 (2018).
pubmed: 30340042 pmcid: 6422358 doi: 10.1016/j.cell.2018.09.027
DeBerardine, M., Booth, G. T., Versluis, P. P. & Lis, J. T. The NELF pausing checkpoint mediates the functional divergence of Cdk9. Nat. Commun. 14, 2762 (2023).
pubmed: 37179384 pmcid: 10182999 doi: 10.1038/s41467-023-38359-y
Aoi, Y. et al. SPT5 stabilization of promoter-proximal RNA polymerase II. Mol. Cell 81, 4413–4424.e4415 (2021).
pubmed: 34480849 pmcid: 8687145 doi: 10.1016/j.molcel.2021.08.006
Robb, C. M. et al. Chemically induced degradation of CDK9 by a proteolysis targeting chimera (PROTAC). Chem. Commun. 53, 7577–7580 (2017).
doi: 10.1039/C7CC03879H
Vos, S. M., Farnung, L., Urlaub, H. & Cramer, P. Structure of paused transcription complex Pol II–DSIF–NELF. Nature 560, 601–606 (2018).
pubmed: 30135580 pmcid: 6245578 doi: 10.1038/s41586-018-0442-2
Alexandra, G. C. et al. Evolution of promoter-proximal pausing enabled a new layer of transcription control. Preprint at bioRxiv https://doi.org/10.1101/2023.02.19.529146 (2023).
Gilchrist, D. A. et al. Pausing of RNA polymerase II disrupts DNA-Specified nucleosome organization to enable precise gene regulation. Cell 143, 540–551 (2010).
pubmed: 21074046 pmcid: 2991113 doi: 10.1016/j.cell.2010.10.004
Raymond, M. H. et al. Live cell tracking of macrophage efferocytosis during Drosophila embryo development in vivo. Science 375, 1182–1187 (2022).
pubmed: 35271315 pmcid: 7612538 doi: 10.1126/science.abl4430
Wang, Y. et al. Mitochondrial fission promotes the continued clearance of apoptotic cells by macrophages. Cell 171, 331–345.e322 (2017).
pubmed: 28942921 pmcid: 5679712 doi: 10.1016/j.cell.2017.08.041
Lara Ordóñez, A. J., Fasiczka, R., Naaldijk, Y. & Hilfiker, S. Rab GTPases in Parkinson’s disease: a primer. Essays Biochem. 65, 961–974 (2021).
pubmed: 34414419 pmcid: 8709891 doi: 10.1042/EBC20210016
Proto, J. D. et al. Regulatory T cells promote macrophage efferocytosis during inflammation resolution. Immunity 49, 666–677.e666 (2018).
pubmed: 30291029 doi: 10.1016/j.immuni.2018.07.015
Maschalidi, S. et al. Targeting SLC7A11 improves efferocytosis by dendritic cells and wound healing in diabetes. Nature 606, 776–784 (2022).
pubmed: 35614212 doi: 10.1038/s41586-022-04754-6
Gerlach, B. D. et al. Efferocytosis induces macrophage proliferation to help resolve tissue injury. Cell Metab. 33, 2445–2463.e2448 (2021).
pubmed: 34784501 pmcid: 8665147 doi: 10.1016/j.cmet.2021.10.015
Meriwether, D. et al. Macrophage COX2 mediates efferocytosis, resolution reprogramming, and intestinal epithelial repair. Cell Mol. Gastroenterol. Hepatol. 13, 1095–1120 (2022).
pubmed: 35017061 pmcid: 8873959 doi: 10.1016/j.jcmgh.2022.01.002
Park, D. et al. BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module. Nature 450, 430–434 (2007).
pubmed: 17960134 doi: 10.1038/nature06329
Brahma, S. & Henikoff, S. The BAF chromatin remodeler synergizes with RNA polymerase II and transcription factors to evict nucleosomes. Nat. Genet. 56, 100–111 (2023).
pubmed: 38049663 pmcid: 10786724 doi: 10.1038/s41588-023-01603-8
Lambert, S. A. et al. The human transcription factors. Cell 172, 650–665 (2018).
pubmed: 29425488 doi: 10.1016/j.cell.2018.01.029
Svaren, J. et al. NAB2, a corepressor of NGFI-A (Egr-1) and Krox20, is induced by proliferative and differentiative stimuli. Mol. Cell. Biol. 16, 3545–3553 (1996).
pubmed: 8668170 pmcid: 231349 doi: 10.1128/MCB.16.7.3545
Swirnoff, A. H. et al. Nab1, a corepressor of NGFI-A (Egr-1), contains an active transcriptional repression domain. Mol. Cell. Biol. 18, 512–524 (1998).
pubmed: 9418898 pmcid: 115883 doi: 10.1128/MCB.18.1.512
Canchi, S. et al. Integrating gene and protein expression reveals perturbed functional networks in Alzheimer’s disease. Cell Rep. 28, 1103–1116.e1104 (2019).
pubmed: 31340147 pmcid: 7503200 doi: 10.1016/j.celrep.2019.06.073
Tourtellotte, W. & Milbrandt, J. Sensory ataxia and muscle spindle agenesis in mice lacking the transcription factor Egr3. Nat. Genet. 20, 87–91 (1998).
pubmed: 9731539 doi: 10.1038/1757
Casano, A. M., Albert, M. & Peri, F. Developmental apoptosis mediates entry and positioning of microglia in the zebrafish brain. Cell Rep. 16, 897–906 (2016).
pubmed: 27425604 doi: 10.1016/j.celrep.2016.06.033
Faronato, M. et al. DMXL2 drives epithelial to mesenchymal transition in hormonal therapy resistant breast cancer through Notch hyper-activation. Oncotarget 6, 22467–22479 (2015).
pubmed: 26093085 pmcid: 4673176 doi: 10.18632/oncotarget.4164
Wang, G. G. et al. Quantitative production of macrophages or neutrophils ex vivo using conditional Hoxb8. Nat. Methods 3, 287–293 (2006).
pubmed: 16554834 doi: 10.1038/nmeth865
Corces, M. R. et al. An improved ATAC-seq protocol reduces background and enables interrogation of frozen tissues. Nat. Methods 14, 959–962 (2017).
pubmed: 28846090 pmcid: 5623106 doi: 10.1038/nmeth.4396
Köster, J. & Rahmann, S. Snakemake—a scalable bioinformatics workflow engine. Bioinformatics 28, 2520–2522 (2012).
pubmed: 22908215 doi: 10.1093/bioinformatics/bts480
Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357–359 (2012).
pubmed: 22388286 pmcid: 3322381 doi: 10.1038/nmeth.1923
Bolger, A. M., Lohse, M. & Usadel, B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30, 2114–2120 (2014).
pubmed: 24695404 pmcid: 4103590 doi: 10.1093/bioinformatics/btu170
Ramírez, F., Dündar, F., Diehl, S., Grüning, B. A. & Manke, T. deepTools: a flexible platform for exploring deep-sequencing data. Nucleic Acids Res. 42, W187–W191 (2014).
pubmed: 24799436 pmcid: 4086134 doi: 10.1093/nar/gku365
Shpynov, O., Dievskii, A., Chernyatchik, R., Tsurinov, P. & Artyomov, M. N. Semi-supervised peak calling with SPAN and JBR genome browser. Bioinformatics 37, 4235–4237 (2021).
pubmed: 34019098 pmcid: 9502234 doi: 10.1093/bioinformatics/btab376
Zhang, Y. et al. Model-based Analysis of ChIP-Seq (MACS). Genome Biol. 9, R137 (2008).
pubmed: 18798982 pmcid: 2592715 doi: 10.1186/gb-2008-9-9-r137
Quinlan, A. R. & Hall, I. M. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841–842 (2010).
pubmed: 20110278 pmcid: 2832824 doi: 10.1093/bioinformatics/btq033
Ross-Innes, C. S. et al. Differential oestrogen receptor binding is associated with clinical outcome in breast cancer. Nature 481, 389–393 (2012).
pubmed: 22217937 pmcid: 3272464 doi: 10.1038/nature10730
Zhu, L. J. et al. ChIPpeakAnno: a Bioconductor package to annotate ChIP-seq and ChIP-chip data. BMC Bioinform. 11, 237 (2010).
doi: 10.1186/1471-2105-11-237
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).
pubmed: 20513432 pmcid: 2898526 doi: 10.1016/j.molcel.2010.05.004
Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013).
pubmed: 23104886 doi: 10.1093/bioinformatics/bts635
Danecek, P. et al. Twelve years of SAMtools and BCFtools. GigaScience 10, giab008 (2021).
pubmed: 33590861 pmcid: 7931819 doi: 10.1093/gigascience/giab008
Anders, S., Pyl, P. T. & Huber, W. HTSeq—a Python framework to work with high-throughput sequencing data. Bioinformatics 31, 166–169 (2015).
pubmed: 25260700 doi: 10.1093/bioinformatics/btu638
Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).
pubmed: 25516281 pmcid: 4302049 doi: 10.1186/s13059-014-0550-8
Julius, J. et al. A rapid, sensitive, scalable method for Precision Run-On sequencing (PRO-seq). Preprint at bioRxiv https://doi.org/10.1101/2020.05.18.102277 (2020).
Reimer, K. A., Mimoso, C. A., Adelman, K. & Neugebauer, K. M. Co-transcriptional splicing regulates 3′ end cleavage during mammalian erythropoiesis. Mol. Cell 81, 998–1012.e1017 (2021).
pubmed: 33440169 pmcid: 8038867 doi: 10.1016/j.molcel.2020.12.018
Smith, T., Heger, A. & Sudbery, I. UMI-tools: modeling sequencing errors in Unique Molecular Identifiers to improve quantification accuracy. Genome Res. 27, 491–499 (2017).
pubmed: 28100584 pmcid: 5340976 doi: 10.1101/gr.209601.116
Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545–15550 (2005).
pubmed: 16199517 pmcid: 1239896 doi: 10.1073/pnas.0506580102
Liberzon, A. et al. Molecular signatures database (MSigDB) 3.0. Bioinformatics 27, 1739–1740 (2011).
pubmed: 21546393 pmcid: 3106198 doi: 10.1093/bioinformatics/btr260
Nüsslein-Volhard, C. The zebrafish issue of Development. Development 139, 4099–4103 (2012).
pubmed: 23093421 doi: 10.1242/dev.085217
Santos, D., Luzio, A. & Coimbra, A. M. Zebrafish sex differentiation and gonad development: a review on the impact of environmental factors. Aquat. Toxicol. 191, 141–163 (2017).
pubmed: 28841494 doi: 10.1016/j.aquatox.2017.08.005
Kimmel, C. B., Ballard, W. W., Kimmel, S. R., Ullmann, B. & Schilling, T. F. Stages of embryonic development of the zebrafish. Dev. Dyn. 203, 253–310 (1995).
pubmed: 8589427 doi: 10.1002/aja.1002030302
Peri, F. & Nüsslein-Volhard, C. Live imaging of neuronal degradation by microglia reveals a role for v0-ATPase a1 in phagosomal fusion in vivo. Cell 133, 916–927 (2008).
pubmed: 18510934 doi: 10.1016/j.cell.2008.04.037
Gray, C. et al. Simultaneous intravital imaging of macrophage and neutrophil behaviour during inflammation using a novel transgenic zebrafish. Thromb. and Haemost. 105, 811–819 (2011).
doi: 10.1160/TH10-08-0525
Villani, A. et al. Clearance by microglia depends on packaging of phagosomes into a unique cellular compartment. Dev. Cell 49, 77–88.e77 (2019).
pubmed: 30880002 doi: 10.1016/j.devcel.2019.02.014
Möller, K. et al. A role for the centrosome in regulating the rate of neuronal efferocytosis by microglia in vivo. eLife 11, e82094 (2022).
pubmed: 36398880 pmcid: 9674339 doi: 10.7554/eLife.82094
Shiau, C. E., Kaufman, Z., Meireles, A. M. & Talbot, W. S. Differential requirement for irf8 in formation of embryonic and adult macrophages in zebrafish. PLoS ONE 10, e0117513 (2015).
pubmed: 25615614 pmcid: 4304715 doi: 10.1371/journal.pone.0117513
Wu, X., Shen, W., Zhang, B. & Meng, A. The genetic program of oocytes can be modified in vivo in the zebrafish ovary. J. Mol. Cell. Biol. 10, 479–493 (2018).
pubmed: 30060229 doi: 10.1093/jmcb/mjy044
Kenyon, A. et al. Active nuclear transcriptome analysis reveals inflammasome-dependent mechanism for early neutrophil response to Mycobacterium marinum. Sci. Rep. 7, 6505 (2017).
pubmed: 28747644 pmcid: 5529371 doi: 10.1038/s41598-017-06099-x

Auteurs

Turan Tufan (T)

Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.

Gamze Comertpay (G)

Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.

Ambra Villani (A)

Department of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.

Geoffrey M Nelson (GM)

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.

Marina Terekhova (M)

Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.

Shannon Kelley (S)

Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.

Pavel Zakharov (P)

Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.

Rochelle M Ellison (RM)

Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.

Oleg Shpynov (O)

Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
JetBrains Research, Munich, Germany.

Michael Raymond (M)

Department of Neuroscience and MIC, University of Virginia, Charlottesville, VA, USA.

Jerry Sun (J)

Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.

Yitan Chen (Y)

Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.

Enno Bockelmann (E)

Department of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.

Marta Stremska (M)

Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.

Lance W Peterson (LW)

Department of Pediatrics, Division of Rheumatology and Immunology, Washington University in St. Louis, St. Louis, MO, USA.

Laura Boeckaerts (L)

Unit for Cell Clearance in Health and Disease, VIB-UGent Center for Inflammation Research and the Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.

Seth R Goldman (SR)

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.

J Iker Etchegaray (JI)

Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.

Maxim N Artyomov (MN)

Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.

Francesca Peri (F)

Department of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.

Kodi S Ravichandran (KS)

Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA. kodi@wustl.edu.
Department of Neuroscience and MIC, University of Virginia, Charlottesville, VA, USA. kodi@wustl.edu.
Unit for Cell Clearance in Health and Disease, VIB-UGent Center for Inflammation Research and the Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium. kodi@wustl.edu.

Classifications MeSH