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 upregulated during monopoiesis and expressed by circulating monocytes, as well as effector monocytes infiltrating certain sites of inflammation, such the spinal cord during experimental autoimmune encephalomyelitis (EAE).  Using competitive in vitro and in vivo assays, we show here 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. SOURCE: Steffen Jung (s.jung@weizmann.ac.il) - Steffen Jung The Weizmann Institute of Science

Pluto Bioinformatics

GSE94546: Autonomous TNF is critical for monocyte survival in steady state and inflammation in vivo