Granulocyte/Macrophage Colony-stimulating Factor-dependent Dendritic Cells Restrain Lean Adipose Tissue Expansion

Pamir, Nathalie; Liu, Ning Chun; Irwin, Angela; Becker, Lev; Peng, Yufeng; Ronsein, Graziella Eliza; Bornfeldt, Karin E.; Duffield, Jeremy S.; Heinecke, Jay W.

doi:10.1074/jbc.m115.645820

Cited by 30 publications

(41 citation statements)

References 55 publications

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“…This group showed that ATDCs accumulate in adipose tissue of HFD-fed mice and in the subcutaneous adipose tissue of obese humans, and blocking their accumulation improves insulin sensitivity in obese mice (Cho et al, 2016). In further support of this action, Jay Heinekcke’s group has produced evidence that dendritic cells constrain healthy expansion of adipose tissue, and depletion of these cells improves glucose homeostasis in lean mice (Pamir et al, 2015). Jerry Olefsky’s laboratory has also demonstrated an important role for neutrophils in obesity-related insulin resistance, showing that genetic deletion of neutrophil elastase reduces macrophage influx into the adipose tissue of obese mice and results in improved insulin sensitivity (Talukdar et al, 2012).…”

Section: Innate Immune Cellular Mediators Of Inflammationmentioning

confidence: 99%

Foundations of Immunometabolism and Implications for Metabolic Health and Disease

2017

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Highly ordered interactions between immune and metabolic responses are evolutionarily conserved and paramount for tissue and organismal health. Disruption of these interactions underlies the emergence of many pathologies, particularly chronic non-communicable diseases such as obesity and diabetes. Here, we examine decades of research identifying the complex immunometabolic signaling networks and the cellular and molecular events that occur in the setting of altered nutrient and energy exposures and offer a historical perspective. Furthermore, we describe recent advances such as the discovery that a broad complement of immune cells play a role in immunometabolism and the emerging evidence that nutrients and metabolites modulate inflammatory pathways. Lastly, we discuss how this work may eventually lead to tangible therapeutic advancements to promote health.

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Section: Innate Immune Cellular Mediators Of Inflammationmentioning

confidence: 99%

Foundations of Immunometabolism and Implications for Metabolic Health and Disease

2017

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“…Medium was replaced on days 4 and 6. Cells were loaded with cholesterol by incubating them overnight in RPMI medium supplemented with 2% plasma harvested from LDL receptor-deficient mice fed a high-fat diet for 16 weeks (64)(65)(66).…”

Section: Methodsmentioning

confidence: 99%

Plasminogen promotes cholesterol efflux by the ABCA1 pathway

et al. 2017

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“…However, since CD11b and F4/80 expression overlaps between macrophages and DCs, it has been difficulty to clarify the contribution of ATDC to adipose tissue inflammation. In mouse obesity models, ATDC have been defined as CD11b + CD11c + , CD11c + F4/80 lo , CD11c + , or CD11c + F4/80 neg-lo cells depending on the study (19–24). Based on these definitions, conventional (cDC) and plasmacytoid (pDC; B220 + ) ATDC have been reported, but how these overlap with the previously defined CD11c + and CD11c − ATM has not been clarified.…”

Section: Introductionmentioning

confidence: 99%

“…Perforin + ATDC can contribute to the regulation of adipose tissue expansion by controlling adipose tissue T cell clonal expansion (23). GM-CSF dependent DCs contribute to adipose tissue expansion in lean animals (24). CD64 − ATDC in perinodal adipose tissue play a role in antigen capture and presentation to lymph nodes, but how this interfaces with metabolic inflammation in obesity is unclear (22).…”

Section: Introductionmentioning

confidence: 99%

Adipose Tissue Dendritic Cells Are Independent Contributors to Obesity-Induced Inflammation and Insulin Resistance

Cho

Zamarron

Muir

et al. 2016

The Journal of Immunology

122

155

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Dynamic changes of adipose tissue leukocytes, including adipose tissue macrophage (ATM) and adipose tissue dendritic cells (ATDC) contribute to obesity-induced inflammation and metabolic disease. However, clear discrimination between ATDC and ATM in adipose tissue has limited progress in the field of immunometabolism. In this study, we utilize CD64 to distinguish ATM and ATDC and investigated the temporal and functional changes in these myeloid populations during obesity. Flow cytometry and immunostaining demonstrated that the definition of ATM as F4/80+CD11b+ cells overlaps with other leukocytes and that CD45+CD64+ is specific for ATM. The expression of core DC genes were enriched in CD11c+CD64− cells (ATDC), while core macrophage genes were enriched in CD45+CD64+ cells (ATM). CD11c+CD64− ATDC expressed MHCII and co-stimulatory receptors and had similar capacity to stimulate CD4+ T cell proliferation as ATM. ATDC were predominantly CD11b+ conventional DCs and made up the bulk of CD11c+ cells in adipose tissue with moderate high fat diet exposure. Mixed chimeric experiments with Ccr2−/− mice demonstrated that high-fat diet (HFD) induced ATM accumulation from monocytes was dependent on CCR2; while ATDC accumulation was less CCR2-dependent. ATDC accumulation during obesity was attenuated in Ccr7−/− mice and was associated with decreased adipose tissue inflammation and insulin resistance. CD45+CD64+ ATM and CD45+CD64−CD11c+ ATDC were identified in human obese adipose tissue and ATDC were increased in subcutaneous adipose tissue compared to omental. These results support a revised strategy for unambiguous delineation of ATM and ATDC and suggests that ATDC are independent contributors to adipose tissue inflammation during obesity.

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Granulocyte/Macrophage Colony-stimulating Factor-dependent Dendritic Cells Restrain Lean Adipose Tissue Expansion

Cited by 30 publications

References 55 publications

Foundations of Immunometabolism and Implications for Metabolic Health and Disease

Foundations of Immunometabolism and Implications for Metabolic Health and Disease

Plasminogen promotes cholesterol efflux by the ABCA1 pathway

Adipose Tissue Dendritic Cells Are Independent Contributors to Obesity-Induced Inflammation and Insulin Resistance

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