Opposing effect of IFNγ and IFNα on expression of NKG2 receptors: Negative regulation of IFNγ on NK cells

Zhang, Cai; Zhang, Jian; Sun, Rui; Feng, Jinzhou; Wei, Haiming; Tian, Zhigang

doi:10.1016/j.intimp.2005.02.003

Cited by 56 publications

(47 citation statements)

References 35 publications

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“…The binding of these two aNKRs to their putative ligands on target cells enhances NK cell cytotoxicity. The involvement of type I IFN in regulating the expression of NKG2 receptors has been previously reported (55), and our results showing the role of M1-secreted IFN-b in increasing the surface levels of NKG2D extend to a human setting a finding already reported for murine NK cells (45). Interestingly, it has been reported that IL-12 is also able to regulate NKG2D expression on NK cells (46) and that STAT3 is involved in the transcriptional regulation of this aNKR (56).…”

Section: Discussionsupporting

confidence: 87%

Priming of Human Resting NK Cells by Autologous M1 Macrophages via the Engagement of IL-1β, IFN-β, and IL-15 Pathways

Mattiola

Pesant

Tentorio

et al. 2015

The Journal of Immunology

101

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The cross talk between NK cells and macrophages is emerging as a major line of defense against microbial infections and tumors. This study reveals a complex network of soluble mediators and cell-to-cell interactions allowing human classically activated (M1) macrophages, but not resting (M0) or alternatively activated (M2) macrophages, to prime resting autologous NK cells. In this article, we show that M1 increase NK cell cytotoxicity by IL-23 and IFN-β-dependent upregulation of NKG2D, IL-1β-dependent upregulation of NKp44, and trans-presentation of IL-15. Moreover, both IFN-β-dependent cis-presentation of IL-15 on NK cells and engagement of the 2B4-CD48 pathway are used by M1 to trigger NK cell production of IFN-γ. The disclosure of these synergic cellular mechanisms regulating the M1-NK cell cross talk provides novel insights to better understand the role of innate immune responses in the physiopathology of tumor biology and microbial infections

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Section: Discussionsupporting

confidence: 87%

Priming of Human Resting NK Cells by Autologous M1 Macrophages via the Engagement of IL-1β, IFN-β, and IL-15 Pathways

Mattiola

Pesant

Tentorio

et al. 2015

The Journal of Immunology

101

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“…IFN-a therefore alters the balance of stimulatory and inhibitory receptors in favor of activation, leading to NK cell-mediated cytotoxicity, whereas IFN-c exerts the opposite effect. 103 We also found similar opposing effects of these two types of interferons on the expression of MICA, the ligand for NKG2D. 104 Cytokine-induced changes in the tumor microenvironment in HCC patients modulate expression of NK cell receptors and their ligands, thus influencing NK cell antitumor responses and HCC progression.…”

Section: Nkr Expression By Activating Cytokinessupporting

confidence: 52%

NK cell receptor imbalance and NK cell dysfunction in HBV infection and hepatocellular carcinoma

et al. 2014

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Hepatocellular carcinoma (HCC) is currently the third leading cause of cancer mortality and a common poor-prognosis malignancy due to postoperative recurrence and metastasis. There is a significant correlation between chronic hepatitis B virus (HBV) infection and hepatocarcinogenesis. As the first line of host defense against viral infections and tumors, natural killer (NK) cells express a large number of immune recognition receptors (NK receptors (NKRs)) to recognize ligands on hepatocytes, liver sinusoidal endothelial cells, stellate cells and Kupffer cells, which maintain the balance between immune response and immune tolerance of NK cells. Unfortunately, the percentage and absolute number of liver NK cells decrease significantly during the development and progression of HCC. The abnormal expression of NK cell receptors and dysfunction of liver NK cells contribute to the progression of chronic HBV infection and HCC and are significantly associated with poor prognosis for liver cancer. In this review, we focus on the role of NK cell receptors in anti-tumor immune responses in HCC, particularly HBV-related HCC. We discuss specifically how tumor cells evade attack from NK cells and how emerging understanding of NKRs may aid the development of novel treatments for HCC. Novel mono-and combination therapeutic strategies that target the NK cell receptor-ligand system may potentially lead to successful and effective immunotherapy in HCC. Keywords: activating receptor; hepatocellular carcinoma; inhibitory receptor; natural killer cell; natural killer receptor INTRODUCTION Hepatocellular carcinoma (HCC) is currently the third leading cause of cancer mortality and a common poor-prognosis malignancy due to postoperative recurrence and metastasis. 1 Common clinical risk factors for HCC include hepatitis B virus (HBV)/hepatitis C virus (HCV) infection, heavy alcohol intake, steatohepatitis and diabetes. 2 Approximately 50% of HCC cases worldwide can be attributed to chronic HBV infection (CHB) and almost 75% of HCC cases occur in developing countries where HBV is endemic. 3,4 According to statistics, older male patients who are infected with HBV genotype C or co-infected with HCV, have high levels of viral load and have been exposed to the aflatoxin, or older male patients who have a family history of HCC tend to have a high risk of developing HCC. [5][6][7] Accumulating clinical and epidemiological evidence shows a significant correlation between chronic HBV infection and hepatocarcinogenesis. However, the underlying mechanisms

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“…The cytotoxicity of NK cells was down-regulated by the negative signal mediated through inhibitory receptors (19). Three inhibitory receptor families are currently known, the killer cell Ig-like receptors (KIR) found in humans, the Ly49 lectin-like receptors found in mice, and the CD94/NKG2A lectin-like receptors shared by humans and mice (20,21). Our results showed a significant increase in the expression of CD94 on NK cells.…”

Section: Discussionmentioning

confidence: 52%

17β-Estradiol Suppresses Cytotoxicity and Proliferative Capacity of Murine Splenic NK1.1+ Cells

Hao

Zhao

et al. 2008

Cell Mol Immunol

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In order to clarify the effects of 17β-estradiol (E2) on natural killer (NK) cells and the possibly regulatory mechanisms, we obtained highly purified and viable NK cells from C57BL/6J mouse spleen by a magnetic cell sorter (MACS). These cells were treated with E2 and then their cytotoxicity and proliferative capacity were examined. To further investigate the mechanisms on the effect of E2 on NK cells, expressions of activationassociated markers (CD69, CD122) and inhibitory receptors (CD94, Ly49), and intracellular cytokine production were analyzed. At last, we performed the cDNA microarray to explore the possible involved genes. We found that E2 could suppress NK cell cytotoxicity and proliferative capacity in vitro. E2 reduced NK cell cytotoxicity and proliferative capacity, which may be through influencing the phenotypes and cytokine expression of NK cells, mainly involving CD94 and IFN-γ. Furthermore, regulation of Stat4, Fyn, Sh2d1a, Eat2, Cd244, Irf1, Runx1, Irf7, Irf5, Esrra and Nr5a1 genes may be related to the cytotoxicity, proliferation and cytokine production of E2-mediated purified NK cells. Cellular & Molecular Immunology. 2008;5(5):357-364.

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Opposing effect of IFNγ and IFNα on expression of NKG2 receptors: Negative regulation of IFNγ on NK cells

Cited by 56 publications

References 35 publications

Priming of Human Resting NK Cells by Autologous M1 Macrophages via the Engagement of IL-1β, IFN-β, and IL-15 Pathways

Priming of Human Resting NK Cells by Autologous M1 Macrophages via the Engagement of IL-1β, IFN-β, and IL-15 Pathways

NK cell receptor imbalance and NK cell dysfunction in HBV infection and hepatocellular carcinoma

17β-Estradiol Suppresses Cytotoxicity and Proliferative Capacity of Murine Splenic NK1.1+ Cells

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