IFNγ and GM-CSF control complementary differentiation programs in the monocyte-to-phagocyte transition during neuroinflammation.
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| Abstract |
During inflammation, Ly6Chi monocytes are rapidly mobilized from the bone marrow (BM) and are recruited into inflamed tissues, where they undergo monocyte-to-phagocyte transition (MTPT). The in vivo developmental trajectories of the MTPT and the contribution of individual cytokines to this process remain unclear. Here, we used a murine model of neuroinflammation to investigate how granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-γ (IFNγ), two type 1 cytokines, controlled MTPT. Using genetic fate mapping, gene targeting and high-dimensional single-cell multiomics analyses, we found that IFNγ was essential for the gradual acquisition of a mature inflammatory phagocyte phenotype in Ly6Chi monocytes, while GM-CSF was required to license interleukin-1β (IL-1β) production, phagocytosis and oxidative burst. These results suggest that the proinflammatory cytokine environment guided MTPT trajectories in the inflamed central nervous system (CNS) and indicated that GM-CSF was the most prominent target for the disarming of monocyte progenies during neuroinflammation.
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| Authors | Ana Amorim, Donatella De Feo, Ekaterina Friebel, Florian Ingelfinger, Cyrill Dimitri Anderfuhren, Sinduya Krishnarajah, Myrto Andreadou, Christina A Welsh, Zhaoyuan Liu, Florent Ginhoux, Melanie Greter, Burkhard Becher |
| Journal | Nature immunology (Nat Immunol) Vol. 23 Issue 2 Pg. 217-228 (02 2022) ISSN: 1529-2916 [Electronic] United States |
| PMID | 35102344 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | © 2022. The Author(s), under exclusive licence to Springer Nature America, Inc. |
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