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Autonomous TNF is critical for in vivo monocyte survival in steady state and inflammation

Wolf, Y; Shemer, A; Polonsky, M; Gross, M; Mildner, A; Yona, S; David, E; ... Jung, S; + view all (2017) Autonomous TNF is critical for in vivo monocyte survival in steady state and inflammation. Journal of Experimental Medicine , 214 (4) pp. 905-917. 10.1084/jem.20160499. Green open access

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Abstract

Monocytes are circulating mononuclear phagocytes, poised to extravasate to sites of inflammation and differentiate into monocyte-derived macrophages and dendritic cells. Tumor necrosis factor (TNF) and its receptors are up-regulated during monopoiesis and expressed by circulating monocytes, as well as effector monocytes infiltrating certain sites of inflammation, such as the spinal cord, during experimental autoimmune encephalomyelitis (EAE). In this study, using competitive in vitro and in vivo assays, we show that monocytes deficient for TNF or TNF receptors are outcompeted by their wild-type counterpart. Moreover, monocyte-autonomous TNF is critical for the function of these cells, as TNF ablation in monocytes/macrophages, but not in microglia, delayed the onset of EAE in challenged animals and was associated with reduced acute spinal cord infiltration of Ly6C(hi) effector monocytes. Collectively, our data reveal a previously unappreciated critical cell-autonomous role of TNF on monocytes for their survival, maintenance, and function.

Type: Article
Title: Autonomous TNF is critical for in vivo monocyte survival in steady state and inflammation
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1084/jem.20160499
Publisher version: https://doi.org/10.1084/jem.20160499
Language: English
Additional information: Copyright © 2017 Wolf et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/1549551
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