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

Yochai Wolf, Anat Shemer, Michal Polonsky, Mor Gross, Alexander Mildner, Simon Yona, Eyal David, Ki Wook Kim, Tobias Goldmann, Ido Amit, Mathias Heikenwalder, Sergei Nedospasov, Marco Prinz, Nir Friedman, Steffen Jung*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

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 Ly6Chi effector monocytes. Collectively, our data reveal a previously unappreciated critical cell-autonomous role of TNF on monocytes for their survival, maintenance, and function.

Original languageAmerican English
Pages (from-to)905-917
Number of pages13
JournalJournal of Experimental Medicine
Volume214
Issue number4
DOIs
StatePublished - 1 Apr 2017
Externally publishedYes

Bibliographical note

Funding Information:
We would like to thank all members of the Jung laboratory for helpful discussion and the staff of the Weizmann Institute animal facility for excellent animal care. Work in the Jung laboratory was supported by the Israel Science Foundation (grant 887/11), the Minerva Foundation (grant 711747), and the European Research Council (AdvERC grant 340345). The authors declare no competing financial interests.

Publisher Copyright:
© 2017 Wolf et al.

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