CCR7 Maintains Nonresolving Lymph Node and Adipose Inflammation in Obesity

Hellmann, Jason; Sansbury, Brian E.; Holden, Candice R.; Tang, Yuanjiao; Wong, Bel; Wysoczynski, Marcin; Rodriguez, Jorge Luis; Bhatnagar, Aruni; Hill, Bradford G.; Spite, Matthew

doi:10.2337/db15-1689

Cited by 34 publications

(39 citation statements)

References 47 publications

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“…Obese patients also have increased C-C chemokine receptor 7 (CCR7) expression in M1 ATM, which perpetuates chronic inflammation. Administration of a monoclonal antibody to CCR7 improved glucose tolerance in mice fed a HFD 167 . There are currently no registered clinical trials on anti-CCR7 therapies.…”

Section: Macrophage and Adipocyte Dysfunction In Obese Adipose Tissuementioning

confidence: 96%

Macrophage functions in lean and obese adipose tissue

2017

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Summary Interactions between macrophages and adipocytes influence both metabolism and inflammation. Obesity-induced changes to macrophages and adipocytes lead to chronic inflammation and insulin resistance. This paper reviews the various functions of macrophages in lean and obese adipose tissue and how obesity alters adipose tissue macrophage phenotypes. Metabolic disease and insulin resistance shift the balance between numerous pro- and anti-inflammatory regulators of macrophages and create a feed-forward loop of increasing inflammatory macrophage activation and worsening adipocyte dysfunction. This ultimately leads to adipose tissue fibrosis and diabetes. The molecular mechanisms underlying these processes have therapeutic implications for obesity, metabolic syndrome, and diabetes.

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Section: Macrophage and Adipocyte Dysfunction In Obese Adipose Tissuementioning

confidence: 96%

Macrophage functions in lean and obese adipose tissue

2017

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“…A recent study showed that infiltration of CCR7-expressing cells in the adipose tissue is associated with insulin resistance in obesity. 22 However, the link between hepatic inflammation and obesity in CCR7-deficient animals had not been reported, and the role of CCR7-expressing immune cells in relation to the development of obesity-associated inflammation has remained unclear until now. CCR7 is a critical molecule for the migration of immune cells to the lymph nodes, and defects in CCR7 have been confirmed to be associated with autoimmune-like inflammation in several organs, including the lachrymal and submandibular glands and the kidney.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to a recent report demonstrating that CCR7 deficiency improved glucose tolerance and insulin sensitivity. 22 CCR7-deficient mice were shown to develop autoimmunity in various organs, 17 and it was proposed that CCR7 −/− mice might carry an increased predisposition for the development of diabetes. In addition, it was shown that the lack of CCR7 induced the dysregulation of mucosal tissue homeostasis and development of autoimmune gastritis and exocrinopathy.…”

Section: Discussionmentioning

confidence: 99%

iNKT cells prevent obesity-induced hepatic steatosis in mice in a C-C chemokine receptor 7-dependent manner

et al. 2017

Int J Obes

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Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are characterized by an increase in hepatic triglyceride content with infiltration of immune cells, which can cause steatohepatitis and hepatic insulin resistance. C-C chemokine receptor 7 (CCR7) is primarily expressed in immune cells, and CCR7 deficiency leads to the development of multi-organ autoimmunity, chronic renal disease and autoimmune diabetes. Here, we investigated the effect of CCR7 on hepatic steatosis in a mouse model and its underlying mechanism. Our results demonstrated that body and liver weights were higher in the CCR7−/− mice than in the wild-type (WT) mice when they were fed a high-fat diet. Further, glucose tolerance and insulin sensitivity were markedly diminished in CCR7−/− mice. The number of invariant natural killer T (iNKT) cells was reduced in the livers of the CCR7−/− mice. Moreover, liver inflammation was detected in obese CCR7−/− mice, which was ameliorated by the adoptive transfer of hepatic mononuclear cells from WT mice, but not through the transfer of hepatic mononuclear cells from CD1d−/− or interleukin-10-deficient (IL-10−/−) mice. Overall, these results suggest that CCR7+ mononuclear cells in the liver could regulate obesity-induced hepatic steatosis via induction of IL-10-expressing iNKT cells.

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“…These evidences indicate that PDK2 may be related to the occurrence and development of pneumonia. In this study, RP11-456D7.1 also positively regulated CCL21 , a high-affinity functional ligand for chemokine receptor 7 (CCR7) that is expressed on T and B lymphocytes and plays a key role in the inflammatory response [ 31 , 32 ]. CCL21 was detected at a significantly higher concentration in the bronchoalveolar lavage fluid of patients with eosinophilic pneumonia than in that of controls [ 33 , 34 ], which is similar to the results of this study.…”

Section: Discussionmentioning

confidence: 99%

Identification of Potential Key Long Non-Coding RNAs and Target Genes Associated with Pneumonia Using Long Non-Coding RNA Sequencing (lncRNA-Seq): A Preliminary Study

Huang

Feng²,

Chen³

et al. 2016

Med Sci Monit

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BackgroundThis study aimed to identify the potential key long non-coding RNAs (lncRNAs) and target genes associated with pneumonia using lncRNA sequencing (lncRNA-seq).Material/MethodsA total of 9 peripheral blood samples from patients with mild pneumonia (n=3) and severe pneumonia (n=3), as well as volunteers without pneumonia (n=3), were received for lncRNA-seq. Based on the sequencing data, differentially expressed lncRNAs (DE-lncRNAs) were identified by the limma package. After the functional enrichment analysis, target genes of DE-lncRNAs were predicted, and the regulatory network was constructed.ResultsIn total, 99 DE-lncRNAs (14 upregulated and 85 downregulated ones) were identified in the mild pneumonia group and 85 (72 upregulated and 13 downregulated ones) in the severe pneumonia group, compared with the control group. Among these DE-lncRNAs, 9 lncRNAs were upregulated in both the mild and severe pneumonia groups. A set of 868 genes were predicted to be targeted by these 9 DE-lncRNAs. In the network, RP11-248E9.5 and RP11-456D7.1 targeted the majority of genes. RP11-248E9.5 regulated several genes together with CTD-2300H10.2, such as QRFP and EPS8. Both upregulated RP11-456D7.1 and RP11-96C23.9 regulated several genes, such as PDK2. RP11-456D7.1 also positively regulated CCL21.ConclusionsThese novel lncRNAs and their target genes may be closely associated with the progression of pneumonia.

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CCR7 Maintains Nonresolving Lymph Node and Adipose Inflammation in Obesity

Cited by 34 publications

References 47 publications

Macrophage functions in lean and obese adipose tissue

Macrophage functions in lean and obese adipose tissue

iNKT cells prevent obesity-induced hepatic steatosis in mice in a C-C chemokine receptor 7-dependent manner

Identification of Potential Key Long Non-Coding RNAs and Target Genes Associated with Pneumonia Using Long Non-Coding RNA Sequencing (lncRNA-Seq): A Preliminary Study

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