Circulating classical monocytes are associated with CD11c+ macrophages in human visceral adipose tissue

Wouters, Kristiaan; Gaens, Katrien; Bijnen, Mitchell; Verboven, Kenneth; Jocken, Johan W. E.; Wetzels, Suzan; Wijnands, Erwin; Hansen, Dominique; Greevenbroek, Marleen M.J. van; Duijvestijn, A. M.; Biessen, Erik A. L.; Blaak, Ellen E.; Stehouwer, Coen D. A.; Schalkwijk, Casper G.

doi:10.1038/srep42665

Cited by 78 publications

(89 citation statements)

References 33 publications

(40 reference statements)

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“…In this regard, the β 2 -integrin family member α X β 2 (CD11c/CD18) has been shown to bind fibrinogen through the γ 390-396 domain and is expressed by monocytes/ macrophages (44,45). Inflammatory CD11c + cells are significantly increased in obese adipose tissue and appear to contribute to the obese phenotype (46)(47)(48).…”

Section: Discussionmentioning

confidence: 99%

Thrombin promotes diet-induced obesity through fibrin-driven inflammation

Kopec

Abrahams

Thornton

et al. 2017

Journal of Clinical Investigation

104

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Section: Discussionmentioning

confidence: 99%

Thrombin promotes diet-induced obesity through fibrin-driven inflammation

Kopec

Abrahams

Thornton

et al. 2017

Journal of Clinical Investigation

104

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“…Several studies reported an increase of the NK cell number in the adipose tissue of leptin-deficient and diet-induced obese mice as well as in the adipose tissue of obese humans (84,107,132,134,135,137,158). This elevated NK cell number is primarily induced by an increased proliferation of tissue-resident NK cells and to a lesser extent by recruitment from the periphery…”

Section: Tissue-resident Nk Cells In Adipose Tissue Of Obese Individualsmentioning

confidence: 99%

Obesity-Associated Alterations of Natural Killer Cells and Immunosurveillance of Cancer

et al. 2020

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Obesity is accompanied by a systemic chronic low-grade inflammation as well as dysfunctions of several innate and adaptive immune cells. Recent findings emphasize an impaired functionality and phenotype of natural killer (NK) cells under obese conditions. This review provides a detailed overview on research related to overweight and obesity with a particular focus on NK cells. We discuss obesity-associated alterations in subsets, distribution, phenotype, cytotoxicity, cytokine secretion, and signaling cascades of NK cells investigated in vitro as well as in animal and human studies. In addition, we provide recent insights into the effects of physical activity and obesity-associated nutritional factors as well as the reduction of body weight and fat mass on NK cell functions of obese individuals. Finally, we highlight the impact of impaired NK cell physiology on obesity-associated diseases, focusing on the elevated susceptibility for viral infections and increased risk for cancer development and impaired treatment response.NK cells are large granular lymphocytes that mediate rapid innate immunity against viruses, bacteria, parasites, and tumor cells without prior sensitization. NK cells primarily develop and mature in the bone marrow, migrate through the bloodstream, and seed into secondary lymphoid organs, like thymus, spleen, and lymph nodes as well as in other peripheral tissues, like lung, liver, kidney, uterus, and the gastrointestinal tract (23). In blood, NK cells represent 1-6% of all leukocytes and comprise up to 15% of human peripheral blood mononuclear cells (PBMCs). Human NK cells have been defined by the expression of adhesion molecule CD56 and by the absence of the T cell marker CD3. Based on their expression level of CD56 and the Fcγ receptor CD16, NK cells are subdivided into different subpopulations. The two major and classically defined subsets are the CD56 dim CD16 bright NK cells and the CD56 bright CD16 dim/neg NK cells. CD56 dim CD16 bright NK cells represent about 90% of all NK cells and are predominantly found in peripheral blood (24). They are mostly responsible for cytotoxic activity and target cell killing but are also a source of pro-inflammatory Abbreviations: ACM, adipocyte-conditioned media; Adamts3, a disintegrin-like and metallopeptidase with thrombospondin type 1 motif, 3; AdipoR, adiponectin receptor; Anxa8, annexin A8; AT, adipose tissue; Bax, Bcl-2-associated X protein; Bcl, B-cell lymphoma; BMI, body mass index; CCR, CC chemokine receptor; Csf1r, colony stimulating factor 1 receptor; CX3CR1, C-X3-C-motif chemokine receptor 1; DNAM-1, DNAX accessory molecule-1; ESR, estrogen receptor; FasL, Fas ligand; IFN-γ, interferon; GM-CSF; granulocyte macrophage colony-stimulating factor; H6pd, hexose-6-phosphate dehydrogenase; Hk2, hexokinase 2; IL, interleukinIL-6R; interleukin-6 receptor; Il18rap, interleukin 18 receptor accessory protein; IP-10, interferon gamma-induced protein 10; JAK, Janus kinase; KIR, killer immunoglobulin-like receptor; Klra1, killer lectin-like receptor subfamil...

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“…Humans and mice have different types of circulating monocytes. The classical subtypes in mouse (Ly‐6G + Ly‐6C high ) and human (CD14 high CD16 − ), which account for ~80% of the circulating monocytes, infiltrate the inflamed tissues and differentiate into inflammatory CD11c + macrophages or DCs . CCL2 (MCP1), which is critical for macrophage‐dependent inflammatory responses in animal models of obesity, binds to the chemokine receptor‐2 (CCR2) and regulates the recruitment of monocyte into the AT .…”

Section: White Adipose Tissue (Wat) In Health and Obesitymentioning

confidence: 99%

“…The classical subtypes in mouse (Ly-6G + Ly-6C high ) and human (CD14 high CD16 − ), which account for~80% of the circulating monocytes, infiltrate the inflamed tissues and differentiate into inflammatory CD11c + macrophages or DCs. [66][67][68] CCL2 (MCP1), which is critical for macrophage-dependent inflammatory responses in animal models of obesity, binds to the chemokine receptor-2 (CCR2) and regulates the recruitment of monocyte into the AT. 69 However, intermediate and non-classical subsets of monocytes (CD16 + CD14 high and CD16 high CD14 dim , respectively) do not express CCR2 but have elevated levels CX3CR1.…”

Section: Monocytes and Macrophagesmentioning

confidence: 99%

An update on immune dysregulation in obesity‐related insulin resistance

2019

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Obesity is associated with chronic low‐grade inflammation of the adipose tissue (AT) that might develop into systemic inflammation, insulin resistance (IR) and an increased risk of type 2 diabetes mellitus (T2DM) in severe obese rodents and humans. In the lean state, small normal adipocytes and AT macrophages interact with each other to maintain metabolic homeostasis but during obesity, enlarged adipocytes secrete inflammatory mediators and express immune receptors to recruit immune cells and aggravate the inflammation. The better understanding of the obesity‐related inflammatory milieu and the sequential events leading to IR could be helpful in designing new preventive and therapeutic strategies. The present review will discuss the cellular and molecular abnormalities participating in the pathogenesis of obesity in obese individuals as well as high‐fat diet (HFD)‐fed mice, a mouse model of obesity.

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Circulating classical monocytes are associated with CD11c+ macrophages in human visceral adipose tissue

Cited by 78 publications

References 33 publications

Thrombin promotes diet-induced obesity through fibrin-driven inflammation

Thrombin promotes diet-induced obesity through fibrin-driven inflammation

Obesity-Associated Alterations of Natural Killer Cells and Immunosurveillance of Cancer

An update on immune dysregulation in obesity‐related insulin resistance

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