NK cells link obesity-induced adipose stress to inflammation and insulin resistance

Wensveen, Felix M.; Jelenčić, Vedrana; Valentić, Sonja; Šestan, Marko; Wensveen, Tamara Turk; Theurich, Sebastian; Glasner, Ariella; Mendrila, Davor; Štimac, Davor; Wunderlich, Frank; Brüning, Jens C.; Mandelboim, Ofer; Polić, Bojan

doi:10.1038/ni.3120

Cited by 419 publications

(488 citation statements)

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“…Using the Ncr1 gfp/gfp mice, it was revealed that Ncr1 is involved in controlling influenza virus infections (5,22,25), tumor and metastases eradication (6,7,10,24), the development of type I and type II diabetes (11,23,26,27), liver fibrosis (28), and bacterial infections (3,29). In all of these studies, the activity of the Ncr1 gfp/gfp NK cells was impaired in an Ncr1-dependent manner.…”

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confidence: 99%

Expression, Function, and Molecular Properties of the Killer Receptor Ncr1-Noé

Glasner¹,

Šimić

Miklić

et al. 2015

The Journal of Immunology

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NK cells kill various cells using activating receptors, such as the natural cytotoxicity receptors (NCRs). NKp46 is a major NCR and is the only NCR expressed in mice (denoted Ncr1). Using Ncr1-deficient mice (Ncr1gfp/pfp) we demonstrated that Ncr1 controls various pathologies, and that in its absence Ncr1-related functions are impaired. In 2012, another Ncr1-related mouse was generated, named Noé, in which a random mutation, W32R, in position 32, impaired the Ncr1-Noé cell surface expression. Interestingly, in the Noé mice, Ncr1-dependent deficiencies were not observed. Additionally, the Noé-NK cells were hyperactivated, probably due to increased Helios expression, and the Noé mice demonstrate increased clearance of influenza and murine CMV. In contrast, in the Ncr1gfp/pfp mice infection with influenza was lethal and we show in the present study no difference in murine CMV infection between Ncr1gfp/pfp and wild-type (WT) mice. Because the foremost difference between the Noé and Ncr1gfp/gfp mice is the presence of a mutated Ncr1-Noé protein, we studied its properties. We show that Ncr1-Noé and various other Ncr1 mutants in position 32 can be expressed on the surface, albeit slowly and unstably, and that ligand recognition and function of the various Ncr1-Noé is similar to the WT Ncr1. We further show that the glycosylation pattern of Ncr1-Noé is aberrant, that the Ncr1-Noé proteins accumulate in the endoplasmic reticulum, and that the expression of Ncr1-Noé proteins, but not WT Ncr1, leads to increased Helios expression. Thus, we suggest that the NK hyperactivated phenotype observed in the Noé mice might result from the presence of the Ncr1-Noé protein.

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confidence: 99%

Expression, Function, and Molecular Properties of the Killer Receptor Ncr1-Noé

Glasner¹,

Šimić

Miklić

et al. 2015

The Journal of Immunology

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“…Studies using rodent models show that obesity-related stress alters immune cell polarization in metabolically active organs such as adipose tissue, pancreas, and liver (9)(10)(11). For example, recent work has highlighted the importance of immunomodulatory factors (i.e., type-2 cytokines) produced by immune cells for maintaining healthy metabolic homeostasis in adipocytes (12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

Maternal obesity drives functional alterations in uterine NK cells

et al. 2016

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“…tumor cells, NK cells can respond to allogeneic, virus-infected, and stressed cells (13,14). NK cells are early potent producers of IFN-γ, a cytokine that plays a key role in tumor immunosurveillance and activates the inflammatory cascade against neoplastic threat (15).…”

Section: Introductionmentioning

confidence: 99%