TY - JOUR
T1 - CCR2 deficiency leads to increased eosinophils, alternative macrophage activation, and type 2 cytokine expression in adipose tissue
AU - Bolus, W. Reid
AU - Gutierrez, Dario A.
AU - Kennedy, Arion J.
AU - Anderson-Baucum, Emily K.
AU - Hasty, Alyssa H.
N1 - Publisher Copyright:
© Society for Leukocyte Biology.
PY - 2015/10
Y1 - 2015/10
N2 - Adipose tissue (AT) inflammation during obesity is medi- ated by immune cells and closely correlates with systemic insulin resistance. In lean AT, eosinophils are present in low but significant numbers and capable of promoting alter- native macrophage activation in an IL-4/IL-13-dependent manner. In WT mice, obesity causes the proportion of AT eosinophils to decline, concomitant with inflammation and classical activation of AT macrophages. In this study, we show that CCR2 deficiency leads to increased eosinophil accumulation in AT. Furthermore, in contrast to WT mice, the increase in eosinophils in CCR2-/- AT is sustained and even amplified during obesity. Interestingly, a significant portion of eosinophils is found in CLSs in AT of obese CCR2-/- mice, which is the first time eosinophils have been shown to localize to these inflammatory hot spots. CCR2-/- bone marrow precursors displayed increased expression of various key eosinophil genes during in vitro differentiation to eosinophils, suggesting a potentially altered eosinophil phenotype in the absence of CCR2. In addition, the proportion of eosinophils in AT positively correlated with local expression of Il5, a potent eosinophil stimulator. The increase in eosinophils in CCR2-/- mice was detected in all white fat pads analyzed and in the peritoneal cavity but not in bone marrow, blood, spleen, or liver. In AT of CCR2-/- mice, an increased eosinophil number positively correlated with M2-like macrophages, expression of the Treg marker Foxp3, and type 2 cytokines, Il4, Il5, and Il13. This is the first study to link CCR2 function with regulation of AT eosinophil accumulation.
AB - Adipose tissue (AT) inflammation during obesity is medi- ated by immune cells and closely correlates with systemic insulin resistance. In lean AT, eosinophils are present in low but significant numbers and capable of promoting alter- native macrophage activation in an IL-4/IL-13-dependent manner. In WT mice, obesity causes the proportion of AT eosinophils to decline, concomitant with inflammation and classical activation of AT macrophages. In this study, we show that CCR2 deficiency leads to increased eosinophil accumulation in AT. Furthermore, in contrast to WT mice, the increase in eosinophils in CCR2-/- AT is sustained and even amplified during obesity. Interestingly, a significant portion of eosinophils is found in CLSs in AT of obese CCR2-/- mice, which is the first time eosinophils have been shown to localize to these inflammatory hot spots. CCR2-/- bone marrow precursors displayed increased expression of various key eosinophil genes during in vitro differentiation to eosinophils, suggesting a potentially altered eosinophil phenotype in the absence of CCR2. In addition, the proportion of eosinophils in AT positively correlated with local expression of Il5, a potent eosinophil stimulator. The increase in eosinophils in CCR2-/- mice was detected in all white fat pads analyzed and in the peritoneal cavity but not in bone marrow, blood, spleen, or liver. In AT of CCR2-/- mice, an increased eosinophil number positively correlated with M2-like macrophages, expression of the Treg marker Foxp3, and type 2 cytokines, Il4, Il5, and Il13. This is the first study to link CCR2 function with regulation of AT eosinophil accumulation.
KW - Inflammation
KW - Interleukin 5
KW - Obesity
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U2 - 10.1189/jlb.3HI0115-018R
DO - 10.1189/jlb.3HI0115-018R
M3 - Article
C2 - 25934927
AN - SCOPUS:84943179861
SN - 0741-5400
VL - 98
SP - 467
EP - 477
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 4
ER -