title: CC-chemokine receptor 7 (CCR7) deficiency alters adipose tissue leukocyte populations in mice.
abstract: The mechanism by which macrophages and other immune cells accumulate in adipose tissue (AT) has been an area of intense investigation over the past decade. Several different chemokines and their cognate receptors have been studied for their role as chemoattractants in promoting recruitment of immune cells to AT However, it is also possible that chemoattractants known to promote clearance of immune cells from tissues to regional lymph nodes might be a critical component to overall AT immune homeostasis. In this study, we evaluated whether CCR7 influences AT macrophage (ATM) or T-cell (ATT) accumulation. CCR7-/-and littermate wild-type (WT) mice were placed on low-fat diet (LFD) or high-fat diet (HFD) for 16 weeks. CCR7 deficiency did not impact HFD-induced weight gain, hepatic steatosis, or glucose intolerance. Although lean CCR7-/-mice had an increased proportion of alternatively activated ATMs, there were no differences in ATM accumulation or polarization between HFD-fed CCR7-/-mice and their WT counterparts. However, CCR7 deficiency did lead to the preferential accumulation of CD8+ATT cells, which was further exacerbated by HFD feeding. Finally, expression of inflammatory cytokines/chemokines, such as Tnf, Il6, Il1β, Ccl2, and Ccl3, was equally elevated in AT by HFD feeding in CCR7-/-and WT mice, while Ifng and Il18 were elevated by HFD feeding in CCR7-/-but not in WT mice. Together, these data suggest that CCR7 plays a role in CD8+ATT cell egress, but does not influence ATM accumulation or the metabolic impact of diet-induced obesity.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Jeb S
authors.initials: JS
authors.lastname: Orr
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Arion J
authors.initials: AJ
authors.lastname: Kennedy
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Hill
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Emily K
authors.initials: EK
authors.lastname: Anderson-Baucum
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Merla J
authors.initials: MJ
authors.lastname: Hubler
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee alyssa.hasty@vanderbilt.edu.
authors.forename: Alyssa H
authors.initials: AH
authors.lastname: Hasty
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D007378:Interleukins / Q000378:metabolism; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D054400:Receptors, CCR7 / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C515371:Ccr7 protein, mouse; D007378:Interleukins; D054400:Receptors, CCR7; D014409:Tumor Necrosis Factor-alpha
keywords: Adipose tissue; CCR7; T cells; macrophages; obesity