Cxcl10
Animals
Autoimmunity
Cell Differentiation
Cells, Cultured
Central Nervous System
Chemokine CXCL10
/ metabolism
Dendritic Cells
/ physiology
Encephalomyelitis, Autoimmune, Experimental
/ immunology
Female
Humans
Mice
Mice, Inbred C57BL
Mice, Transgenic
Monocytes
/ physiology
Multiple Sclerosis
/ immunology
Neurogenic Inflammation
Phagocytes
/ physiology
Serum Amyloid A Protein
/ metabolism
Single-Cell Analysis
Transcription Factors
/ genetics
Journal
Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
28
05
2019
accepted:
13
03
2020
pubmed:
22
4
2020
medline:
7
7
2020
entrez:
22
4
2020
Statut:
ppublish
Résumé
Multiple sclerosis (MS) is characterized by pathological inflammation that results from the recruitment of lymphoid and myeloid immune cells from the blood into the brain. Due to subset heterogeneity, defining the functional roles of the various cell subsets in acute and chronic stages of MS has been challenging. Here, we used index and transcriptional single-cell sorting to characterize the mononuclear phagocytes that infiltrate the central nervous system from the periphery in mice with experimentally induced autoimmune encephalomyelitis, a model of MS. We identified eight monocyte and three dendritic cell subsets at acute and chronic disease stages in which the defined transcriptional programs pointed toward distinct functions. Monocyte-specific cell ablation identified Cxcl10
Identifiants
pubmed: 32313246
doi: 10.1038/s41590-020-0661-1
pii: 10.1038/s41590-020-0661-1
doi:
Substances chimiques
Chemokine CXCL10
0
Saa3 protein, mouse
0
Serum Amyloid A Protein
0
Transcription Factors
0
Zbtb46 protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
525-534Subventions
Organisme : Howard Hughes Medical Institute
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : ErratumIn
Type : ErratumIn
Références
Geissmann, F., Jung, S. & Littman, D. R. Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 19, 71–82 (2003).
pubmed: 12871640
Carlin, L. M. et al. Nr4a1-dependent Ly6C
pubmed: 23582326
pmcid: 3898614
Mildner, A., Yona, S. & Jung, S. A close encounter of the third kind: monocyte-derived cells. Adv. Immunol. 120, 69–103 (2013).
pubmed: 24070381
Mildner, A. et al. Genomic characterization of murine monocytes reveals C/EBPβ transcription factor dependence of Ly6C
pubmed: 28514690
Menezes, S. et al. The heterogeneity of Ly6C
pubmed: 28002729
pmcid: 5196026
Yáñez, A. et al. Granulocyte-monocyte progenitors and monocyte-dendritic cell progenitors independently produce functionally distinct monocytes. Immunity 47, 890–902.e4 (2017).
pubmed: 29166589
pmcid: 5726802
Liu, Z. et al. Fate mapping via Ms4a3-expression history traces monocyte-derived cells. Cell 178, 1509–1525.e19 (2019).
pubmed: 31491389
Mildner, A. et al. CCR2
pubmed: 19531531
King, I. L., Dickendesher, T. L. & Segal, B. M. Circulating Ly-6C
pubmed: 19196868
pmcid: 2665891
Ajami, B., Bennett, J. L., Krieger, C., McNagny, K. M. & Rossi, F. M. V. Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool. Nat. Neurosci. 14, 1142–1149 (2011).
pubmed: 21804537
Croxford, A. L. et al. The cytokine GM-CSF drives the inflammatory signature of CCR2
pubmed: 26341401
Spath, S. et al. Dysregulation of the cytokine GM-CSF induces spontaneous phagocyte invasion and immunopathology in the central nervous system. Immunity 46, 245–260 (2017).
pubmed: 28228281
Jaitin, D. A. et al. Massively parallel single-cell RNA-seq for marker-free decomposition of tissues into cell types. Science 343, 776–779 (2014).
pubmed: 24531970
pmcid: 4412462
Locatelli, G. et al. Mononuclear phagocytes locally specify and adapt their phenotype in a multiple sclerosis model. Nat. Neuroscience. 21, 1196–1208 (2018).
pubmed: 30127427
Caravagna, C. et al. Diversity of innate immune cell subsets across spatial and temporal scales in an EAE mouse model. Sci. Rep. 8, 5146 (2018).
pubmed: 29572472
pmcid: 5865173
Lewis, N. D., Hill, J. D., Juchem, K. W., Stefanopoulos, D. E. & Modis, L. K. RNA sequencing of microglia and monocyte-derived macrophages from mice with experimental autoimmune encephalomyelitis illustrates a changing phenotype with disease course. J. Neuroimmunol. 277, 26–38 (2014).
pubmed: 25270668
Giladi, A. et al. Single-cell characterization of haematopoietic progenitors and their trajectories in homeostasis and perturbed haematopoiesis. Nat. Cell Biol. 20, 836–846 (2018).
pubmed: 29915358
pmcid: 29915358
Baran, Y. et al. MetaCell: analysis of single-cell RNA-seq data using K-nn graph partitions. Genome Biol. 20, 206–219 (2019).
pubmed: 31604482
pmcid: 6790056
Butler, A., Hoffman, P., Smibert, P., Papalexi, E. & Satija, R. Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat. Biotechnol. 36, 411–420 (2018).
pubmed: 6700744
pmcid: 6700744
Meredith, M. M. et al. Zinc finger transcription factor zDC is a negative regulator required to prevent activation of classical dendritic cells in the steady state. J. Exp. Med. 209, 1583–1593 (2012).
pubmed: 22851594
pmcid: 3428942
Satpathy, A. T. et al. Zbtb46 expression distinguishes classical dendritic cells and their committed progenitors from other immune lineages. J. Exp. Med. 209, 1135–1152 (2012).
pubmed: 22615127
pmcid: 3371733
Briseño, C. G. et al. Distinct transcriptional programs control cross-priming in classical and monocyte-derived dendritic cells. Cell Rep. 15, 2462–2474 (2016).
pubmed: 27264183
pmcid: 4941620
Wolf, Y. et al. Microglial MHC class II is dispensable for experimental autoimmune encephalomyelitis and cuprizone-induced demyelination. Eur. J. Immunol. 48, 1308–1318 (2018).
pubmed: 29697861
Brühl, H. et al. Targeting of Gr-1
pubmed: 17763443
Varol, C. et al. Monocytes give rise to mucosal, but not splenic, conventional dendritic cells. J. Exp. Med. 204, 171–180 (2007).
pubmed: 17190836
pmcid: 2118434
Matcovitch-Natan, O. et al. Microglia development follows a stepwise program to regulate brain homeostasis. Science 353, aad8670 (2016).
pubmed: 27338705
Shemer, A. et al. Engrafted parenchymal brain macrophages differ from microglia in transcriptome, chromatin landscape and response to challenge. Nat. Commun. 9, 5206 (2018).
pubmed: 30523248
pmcid: 6284018
Becher, B., Tugues, S. & Greter, M. GM-CSF: from growth factor to central mediator of tissue inflammation. Immunity 45, 963–973 (2016).
pubmed: 27851925
pmcid: 27851925
Esiri, M. M. & Reading, M. C. Macrophage populations associated with multiple sclerosis plaques. Neuropathol. Appl. Neurobiol. 13, 451–465 (1987).
pubmed: 3328828
Brück, W. et al. Monocyte/macrophage differentiation in early multiple sclerosis lesions. Ann. Neurol. 38, 788–796 (1995).
pubmed: 7486871
Melero-Jerez, C., Ortega, M. C., Moliné-Velázquez, V. & Clemente, D. Myeloid derived suppressor cells in inflammatory conditions of the central nervous system. Biochim. Biophys. Acta. 1862, 368–380 (2016).
pubmed: 26527182
McQualter, J. L. et al. Granulocyte macrophage colony-stimulating factor: a new putative therapeutic target in multiple sclerosis. J. Exp. Med. 194, 873–882 (2001).
pubmed: 2193476
pmcid: 2193476
Greter, M. et al. GM-CSF controls nonlymphoid tissue dendritic cell homeostasis but is dispensable for the differentiation of inflammatory dendritic cells. Immunity 36, 1031–1046 (2012).
pubmed: 22749353
pmcid: 3498051
Blecher-Gonen, R. et al. Single-cell analysis of diverse pathogen responses defines a molecular roadmap for generating antigen-specific immunity. Cell Syst. 8, 109–121.e6 (2019).
pubmed: 30772378
Hirako, I. C. et al. Splenic differentiation and emergence of CCR5
pubmed: 27808089
pmcid: 5097164
Serbina, N. V., Salazar-Mather, T. P., Biron, C. A., Kuziel, W. A. & Pamer, E. G. TNF/iNOS-producing dendritic cells mediate innate immune defense against bacterial infection. Immunity 19, 59–70 (2003).
pubmed: 12871639
Paré, A. et al. IL-1β enables CNS access to CCR2
pubmed: 29358392
pmcid: 5819409
Ronchi, F. et al. Experimental priming of encephalitogenic Th1/Th17 cells requires pertussis toxin-driven IL-1β production by myeloid cells. Nat. Commun. 7, 11541 (2016).
pubmed: 27189410
pmcid: 4873938
Fife, B. T. et al. CXCL10 (IFN-γ-inducible protein-10) control of encephalitogenic CD4
pubmed: 11390519
Zilionis, R. et al. Single-cell transcriptomics of human and mouse lung cancers reveals conserved myeloid populations across individuals and species. Immunity 50, 1317–1334 (2019).
pubmed: 30979687
pmcid: 6620049
Cohen, M. et al. Lung single-cell signaling interaction map reveals basophil role in macrophage imprinting. Cell 175, 1031–1044.e18 (2018).
pubmed: 30318149
Hettinger, J. et al. Origin of monocytes and macrophages in a committed progenitor. Nat. Immunol. 14, 821–830 (2013).
pubmed: 23812096
Kim, D., Langmead, B. & Salzberg, S. L. HISAT: a fast spliced aligner with low memory requirements. Nat. Methods. 12, 357–360 (2015).
pubmed: 25751142
pmcid: 4655817
Yu, G., Wang, L.-G., Han, Y. & He, Q.-Y. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS 16, 284–287 (2012).
pubmed: 22455463
pmcid: 3339379
Supek, F., Bošnjak, M., Škunca, N. & Šmuc, T. REVIGO summarizes and visualizes long lists of gene ontology terms. PLoS ONE 6, e21800 (2011).
pubmed: 21789182
pmcid: 3138752