IGF1 Shapes Macrophage Activation in Response to Immunometabolic Challenge
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IGF1 Shapes Macrophage Activation in Response to Immunometabolic Challenge. / Spadaro, Olga; Camell, Christina D; Bosurgi, Lidia; Nguyen, Kim Y; Youm, Yun-Hee; Rothlin, Carla V; Dixit, Vishwa Deep.
In: CELL REP, Vol. 19, No. 2, 11.04.2017, p. 225-234.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - IGF1 Shapes Macrophage Activation in Response to Immunometabolic Challenge
AU - Spadaro, Olga
AU - Camell, Christina D
AU - Bosurgi, Lidia
AU - Nguyen, Kim Y
AU - Youm, Yun-Hee
AU - Rothlin, Carla V
AU - Dixit, Vishwa Deep
N1 - Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
PY - 2017/4/11
Y1 - 2017/4/11
N2 - In concert with their phagocytic activity, macrophages are thought to regulate the host immunometabolic responses primarily via their ability to produce specific cytokines and metabolites. Here, we show that IL-4-differentiated, M2-like macrophages secrete IGF1, a hormone previously thought to be exclusively produced from liver. Ablation of IGF1 receptors from myeloid cells reduced phagocytosis, increased macrophages in adipose tissue, elevated adiposity, lowered energy expenditure, and led to insulin resistance in mice fed a high-fat diet. The investigation of adipose macrophage phenotype in obese myeloid IGF1R knockout (MIKO) mice revealed a reduction in transcripts associated with M2-like macrophage activation. Furthermore, the MIKO mice infected with helminth Nippostrongylus brasiliensis displayed delayed resolution from infection with normal insulin sensitivity. Surprisingly, cold challenge did not trigger an overt M2-like state and failed to induce tyrosine hydroxylase expression in adipose tissue macrophages of control or MIKO mice. These results show that IGF1 signaling shapes the macrophage-activation phenotype.
AB - In concert with their phagocytic activity, macrophages are thought to regulate the host immunometabolic responses primarily via their ability to produce specific cytokines and metabolites. Here, we show that IL-4-differentiated, M2-like macrophages secrete IGF1, a hormone previously thought to be exclusively produced from liver. Ablation of IGF1 receptors from myeloid cells reduced phagocytosis, increased macrophages in adipose tissue, elevated adiposity, lowered energy expenditure, and led to insulin resistance in mice fed a high-fat diet. The investigation of adipose macrophage phenotype in obese myeloid IGF1R knockout (MIKO) mice revealed a reduction in transcripts associated with M2-like macrophage activation. Furthermore, the MIKO mice infected with helminth Nippostrongylus brasiliensis displayed delayed resolution from infection with normal insulin sensitivity. Surprisingly, cold challenge did not trigger an overt M2-like state and failed to induce tyrosine hydroxylase expression in adipose tissue macrophages of control or MIKO mice. These results show that IGF1 signaling shapes the macrophage-activation phenotype.
KW - Adipose Tissue
KW - Adiposity
KW - Animals
KW - Cell Differentiation
KW - Diet, High-Fat
KW - Insulin Resistance
KW - Insulin-Like Growth Factor I
KW - Interleukin-4
KW - Macrophages
KW - Mice
KW - Mice, Knockout
KW - Nippostrongylus
KW - Phagocytosis
KW - Signal Transduction
KW - Strongylida Infections
KW - Journal Article
U2 - 10.1016/j.celrep.2017.03.046
DO - 10.1016/j.celrep.2017.03.046
M3 - SCORING: Journal article
C2 - 28402847
VL - 19
SP - 225
EP - 234
JO - CELL REP
JF - CELL REP
SN - 2211-1247
IS - 2
ER -