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Publication : mTORC2 Signaling Selectively Regulates the Generation and Function of Tissue-Resident Peritoneal Macrophages.

First Author  Oh MH Year  2017
Journal  Cell Rep Volume  20
Issue  10 Pages  2439-2454
PubMed ID  28877476 Mgi Jnum  J:254940
Mgi Id  MGI:6103935 Doi  10.1016/j.celrep.2017.08.046
Citation  Oh MH, et al. (2017) mTORC2 Signaling Selectively Regulates the Generation and Function of Tissue-Resident Peritoneal Macrophages. Cell Rep 20(10):2439-2454
abstractText  Tissue-resident macrophages play critical roles in sentinel and homeostatic functions as well as in promoting inflammation and immunity. It has become clear that the generation of these cells is highly dependent upon tissue-specific cues derived from the microenvironment that, in turn, regulate unique differentiation programs. Recently, a role for GATA6 has emerged in the differentiation programming of resident peritoneal macrophages. We identify a critical role for mTOR in integrating cues from the tissue microenvironment in regulating differentiation and metabolic reprogramming. Specifically, inhibition of mTORC2 leads to enhanced GATA6 expression in a FOXO1 dependent fashion. Functionally, inhibition of mTORC2 promotes peritoneal resident macrophage generation in the resolution phase during zymosan-induced peritonitis. Also, mTORC2-deficient peritoneal resident macrophages displayed increased functionality and metabolic reprogramming. Notably, mTORC2 activation distinguishes tissue-resident macrophage proliferation and differentiation from that of M2 macrophages. Overall, our data implicate a selective role for mTORC2 in the differentiation of tissue-resident macrophages.
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