Adiponectin Is a Negative Regulator of NK Cell Cytotoxicity

Kim, Kun Yong; Kim, Jae Kwang; Han, Seung Hyun; Lim, Jong Seok; Kim, Keun Il; Cho, Dae Ho; Lee, Myeong Sok; Lee, Jeong Hyung; Yoon, Do Young; Yoon, Suk Ran; Chung, Jin Woong; Choi, Inpyo; Kim, Eunjoon; Yang, Young

doi:10.4049/jimmunol.176.10.5958

Cited by 110 publications

(97 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We can only speculate that the enhanced function of NK cells we observe upon infection in APN-KO mice is due to the lack of an inhibition by APN but may also reflect a slower NK-cell response upon infection. We could show in vitro that preincubation of murine NK cells with APN diminished TLR-7/8 ligand-induced IFN-γ expression as already described by Kim et al [16].…”

Section: Discussionsupporting

confidence: 57%

“…A previous study by Kim et al [16] already described APN as a negative regulator of NK-cell cytotoxicity and IFN-γ production in murine NK cells. We identified a major difference between human and murine NK-cell surface AdipoR expression, which we observed only on a minor subset of resting murine NK cells.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Few instances of largely conflicting data have been published regarding the regulation of NK-cell function and generation by APN. In one study APN was shown to suppress IL-2-induced NK-cell cytotoxicity in mice [16], whereas O'Shea et al [17] described APN as an inducer of cytotoxicity in lean human subjects.In the present study the expression of AdipoRs and the role of APN in NK-cell function in humans and mice were analyzed. Furthermore, the role of APN on NK-cell function during viral infection was assessed by comparing NK-cell function in WT and adiponectin knockout (APN-KO) mice upon CVB3 infection.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Adiponectin modulates NK‐cell function

et al. 2013

View full text Add to dashboard Cite

Adiponectin (APN) has been shown to exert antiinflammatory effects in various disease models but little is known concerning its regulation of NK-cell function. Here, weshow that the majority of human CD56 dim NK cells express surface Adiponectin receptor (AdipoR) 1 and 2 while most CD56 high NK cells are AdipoR-negative. Toll-like receptor (TLR) ligand-induced IFN-γ production was diminished by APN while it had no influence on NK-cell cytotoxicity. In contrast only a small subpopulation of murine NK cells expresses surface AdipoRs, but about 90% store them intracellularly. APN-deficient knockout (KO) mice had elevated frequencies of NK cells. However, cytotoxic degranulation of NK cells was decreased in APN knockout (APN-KO) animals. Accordingly, frequencies of CD11b high CD27 high and CD94 high effector NK cells and expression of NKG2D were lower in APN-KO mice. Upon CVB3 infection NK-cell function was restored in APN-KO mice. Our data suggest that in addition to its antiinflammatory effects APN also influences the numerical and differentiation status of NK cells, which may further impact the outcome of immune-mediated diseases in APN-KO mice.Keywords: Adiponectin r Adiponectin KO mice r Adiponectin receptors 1 or 2 r Immunomodulation r NK cells Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionAdiponectin (APN), a cytokine, accounting for 0.01% of total plasma protein, is mainly produced by adipocytes under steadystate conditions and negatively regulated by obesity [1,2]. Adiponectin has been shown to exert antiinflammatory effects in several disease models such as sepsis, inflammatory diseases, and Correspondence: Prof. Carmen Scheibenbogen e-mail: Carmen.Scheibenbogen@charite.de transplantation. In accordance, APN-deficient mice are more prone to transplant rejection and inflammatory diseases [3][4][5].APN signaling is mediated by two receptors, adiponectin receptor (AdipoR) 1 and 2, with different affinities for existing isoforms. AdipoR1 is ubiquitous, but most prominent in skeletal muscle and heart, whereas AdipoR2 is abundantly expressed in the liver [6]. AdipoRs expression was further described in cells of the immune system [7,8]. Several studies revealed the direct action of APN on cells of the innate and adaptive immune system [1,9]. APN was shown to inhibit TLR-mediated NF-κB activation in macrophageswww.eji-journal.eu Eur. J. Immunol. 2013. 43: 1024-1033 Immunomodulation 1025[10] and to induce macrophage polarization toward the antiinflammatory M2 phenotype [11]. In a recent study we could further demonstrate that T cells store AdipoRs intracellularly, upregulate them upon T-cell receptor activation, and that APN acts as a negative T-cell regulator for antigen-activated T cells [8]. Furthermore, APN has been described as a negative regulator of hematopoiesis inhibiting directly proliferation of myelomonocytic progenitors [12] or indirectly through inducing changes in stromal cells [13]. NK cells are innate effector lymphocyte...

show abstract

Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Adiponectin modulates NK‐cell function

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Adiponectin inhibits proinflammatory cytokines and endothelial adhesion molecules and induces antiinflammatory cytokines (8)(9)(10)(11). Further, adiponectin regulates the proliferation and function of inflammatory cells including NK cells and T lymphocytes (12,13).…”

mentioning

confidence: 99%

Low Serum Adiponectin Predicts Future Risk for Asthma in Women

Sood¹,

Qualls

Schuyler³

et al. 2012

Am J Respir Crit Care Med

View full text Add to dashboard Cite

Rationale: Our previous cross-sectional study showed that serum adiponectin is inversely associated with asthma among women. However, it is not known if serum adiponectin predicts future development of asthma or if asthma affects subsequent serum adiponectin concentrations among women. Objectives: To determine longitudinal association between serum adiponectin and incident asthma among women. Methods: We used data from examinations at Years 10, 15, and 20 of the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. In our primary analysis, the association of CARDIA Year 15 serum adiponectin concentration with Year 20 incident asthma was evaluated. In our secondary analysis, the converse direction, that is, the association of CARDIA Year 10 prevalent asthma with Year 15 serum adiponectin, was evaluated, using logistic regression techniques. Measurements and Main Results: Our primary analysis included 1,450 women, mostly premenopausal. Multivariable analyses demonstrated that the lowest tertile of Year 15 serum adiponectin concentration (,7 mg/L) predicted significantly higher risk for incident asthma at Year 20 among women (odds ratio, 2.07; 95% confidence interval, 1.05, 4.10), and particularly among current smokers (interaction P ¼ 0.051). Further, low serum adiponectin was more important than body mass index in predicting the risk for incident asthma among women. We also showed that the converse relationship was not true; that is, Year 10 prevalent asthma did not predict Year 15 serum adiponectin concentrations in women. Conclusions: Serum adiponectin affects future risk for asthma in women and not vice versa. Measures that raise systemic adiponectin concentrations may lead to newer ways to prevent asthma among women, particularly among those who smoke.Keywords: incident asthma; obesity; adiponectin; adipokine; women In 2005, more than 21 million people in the United States were estimated to be affected by asthma, amounting to 7.6% of the total population (1). Between 1980 and 1996, the prevalence of, and morbidity trends related to, asthma increased in the United States (2, 3). It is now well established that asthma is related to adiposity, particularly among women. Adipokines, proteins produced by adipose tissue, may regulate systemic inflammation and play a role in asthma (4-7). Adiponectin is one such adipokine with predominantly antiinflammatory effects. Adiponectin inhibits proinflammatory cytokines and endothelial adhesion molecules and induces antiinflammatory cytokines (8-11). Further, adiponectin regulates the proliferation and function of inflammatory cells including NK cells and T lymphocytes (12, 13).Although visceral adipocytes are the most important source of adiponectin, serum adiponectin concentrations are reduced in obese subjects (14,15). One possible explanation is that hypoxia-related necrosis of adipocytes activates macrophages in obese subjects (16). These activated macrophages produce tumor necrosis factor-a and IL-6, which in turn may directly inhibit the local production o...

show abstract

Contribution of Inflammation, Adiponectin, and Obesity in Cardiovascular Diseases

Mangge¹,

Almer²

2013

Metabolic Syndrome and Neurological Disorders

View full text Add to dashboard Cite

Adiponectin Is a Negative Regulator of NK Cell Cytotoxicity

Cited by 110 publications

References 39 publications

Adiponectin modulates NK‐cell function

Adiponectin modulates NK‐cell function

Low Serum Adiponectin Predicts Future Risk for Asthma in Women

Contribution of Inflammation, Adiponectin, and Obesity in Cardiovascular Diseases

Contact Info

Product

Resources

About