Sanin, David E., Ge, Yan ORCID: 0000-0003-2001-3514, Marinkovic, Emilija, Kabat, Agnieszka M., Castoldi, Angela ORCID: 0000-0002-8434-7989, Caputa, George, Grzes, Katarzyna M., Curtis, Jonathan D., Thompson, Elizabeth A., Willenborg, Sebastian ORCID: 0000-0002-0840-227X, Dichtl, Stefanie ORCID: 0000-0002-7657-329X, Reinhardt, Susanne, Dahl, Andreas, Pearce, Erika L., Eming, Sabine A., Gerbaulet, Alexander, Roers, Axel, Murray, Peter J. and Pearce, Edward J. (2022). A common framework of monocyte-derived macrophage activation. Sci. Immunol., 7 (70). WASHINGTON: AMER ASSOC ADVANCEMENT SCIENCE. ISSN 2470-9468

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Abstract

Macrophages populate every organ during homeostasis and disease, displaying features of tissue imprinting and heterogeneous activation. The disconnected picture of macrophage biology that has emerged from these observations is a barrier for integration across models or with in vitro macrophage activation paradigms. We set out to contextualize macrophage heterogeneity across mouse tissues and inflammatory conditions, specifically aiming to define a common framework of macrophage activation. We built a predictive model with which we mapped the activation of macrophages across 12 tissues and 25 biological conditions, finding a notable commonality and finite number of transcriptional profiles, in particular among infiltrating macrophages, which we modeled as defined stages along four conserved activation paths. These activation paths include a phagocytic regulatory path, an inflammatory cytokine-producing path, an oxidative stress antimicrobial path, or a remodeling extracellular matrix deposition path. We verified this model with adoptive cell transfer experiments and identified transient RELM. expression as a feature of monocyte-derived macrophage tissue engraftment. We propose that this integrative approach of macrophage classification allows the establishment of a common predictive framework of monocyte-derived macrophage activation in inflammation and homeostasis.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Sanin, David E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ge, YanUNSPECIFIEDorcid.org/0000-0003-2001-3514UNSPECIFIED
Marinkovic, EmilijaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kabat, Agnieszka M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Castoldi, AngelaUNSPECIFIEDorcid.org/0000-0002-8434-7989UNSPECIFIED
Caputa, GeorgeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grzes, Katarzyna M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Curtis, Jonathan D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thompson, Elizabeth A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Willenborg, SebastianUNSPECIFIEDorcid.org/0000-0002-0840-227XUNSPECIFIED
Dichtl, StefanieUNSPECIFIEDorcid.org/0000-0002-7657-329XUNSPECIFIED
Reinhardt, SusanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dahl, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pearce, Erika L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eming, Sabine A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gerbaulet, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roers, AxelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Murray, Peter J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pearce, Edward J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-687423
DOI: 10.1126/sciimmunol.abl7482
Journal or Publication Title: Sci. Immunol.
Volume: 7
Number: 70
Date: 2022
Publisher: AMER ASSOC ADVANCEMENT SCIENCE
Place of Publication: WASHINGTON
ISSN: 2470-9468
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GENE-EXPRESSION; MAST-CELLS; INFLAMMATION; DIVERSITY; LANDSCAPES; IDENTITY; NICHE; MODELMultiple languages
ImmunologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/68742

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