TY - JOUR
T1 - Autonomous TNF is critical for in vivo monocyte survival in steady state and inflammation
AU - Wolf, Yochai
AU - Shemer, Anat
AU - Polonsky, Michal
AU - Gross, Mor
AU - Mildner, Alexander
AU - Yona, Simon
AU - David, Eyal
AU - Kim, Ki Wook
AU - Goldmann, Tobias
AU - Amit, Ido
AU - Heikenwalder, Mathias
AU - Nedospasov, Sergei
AU - Prinz, Marco
AU - Friedman, Nir
AU - Jung, Steffen
N1 - Publisher Copyright:
© 2017 Wolf et al.
PY - 2017/4/1
Y1 - 2017/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85020306033&partnerID=8YFLogxK
U2 - 10.1084/jem.20160499
DO - 10.1084/jem.20160499
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C2 - 28330904
AN - SCOPUS:85020306033
SN - 0022-1007
VL - 214
SP - 905
EP - 917
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 4
ER -