Oxygen tension regulates NK cells differentiation from hematopoietic stem cells in vitro

Yun, Sohyun; Lee, Suk Hyung; Yoon, Suk-Ran; Myung, Pyung-Keun; Choi, Inpyo

doi:10.1016/j.imlet.2011.02.020

Cited by 12 publications

(10 citation statements)

References 40 publications

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“…Although the effect of hypoxia on tumour immune escape remains poorly understood, substantial evidence suggests that hypoxia might affect the phenotype and activity of monocytes and natural killer (NK) cells [16], which are crucial for driving a potent immune response. In turn, oxygen plays a critical role in NK cell development [17], modulating important transcription factors (RAR-related orphan receptor C (RORC), T-Box protein 21 (Tbet) and eomesodermin (EOMES)) involved in the late stages of NK cell maturation [18]. It has also been reported that transforming growth factor β (TGF-β) modulates NK differentiation and cytotoxicity via the SMAD3 pathway [19,20].…”

Section: Introductionmentioning

confidence: 99%

Monocytes inhibit NK activityviaTGF-β in patients with obstructive sleep apnoea

et al. 2017

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Obstructive sleep apnoea (OSA) is associated with cancer incidence and mortality. The contribution of the immune system appears to be crucial; however, the potential role of monocytes and natural killer (NK) cells remains unclear.Quantitative reverse transcriptase PCR, flow cytometry and assays were used to analyse the phenotype and immune response activity in 92 patients with OSA (60 recently diagnosed untreated patients and 32 patients after 6 months of treatment with continuous positive airway pressure (CPAP)) and 29 healthy volunteers (HV).We determined that monocytes in patients with OSA exhibit an immunosuppressive phenotype, including surface expression of glycoprotein-A repetitions predominant protein (GARP) and transforming growth factor-β (TGF-β), in contrast to those from the HV and CPAP groups. High levels of TGF-β were detected in OSA sera. TGF-β release by GARP monocytes impaired NK cytotoxicity and maturation. This altered phenotype correlated with the hypoxic severity clinical score (CT90). Reoxygenation eventually restored the altered phenotypes and cytotoxicity.This study demonstrates that GARP monocytes from untreated patients with OSA have an NK-suppressing role through their release of TGF-β. Our findings show that monocyte plasticity immunomodulates NK activity in this pathology, suggesting a potential role in cancer incidence.

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Section: Introductionmentioning

confidence: 99%

Monocytes inhibit NK activityviaTGF-β in patients with obstructive sleep apnoea

et al. 2017

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“…Furthermore, both pro‐ and antiapoptotic consequences of hypoxia have been documented depending on the cellular context , resulting in cell death , or survival of distinct immune cell populations. Recent evidences indicate that low pO 2 can affect NK‐cell differentiation from hematopoietic stem cells in vitro . Limited information, however, is currently available on the impact of hypoxia on mature, ready to kill, NK cells.…”

Section: Introductionmentioning

confidence: 99%

Hypoxia downregulates the expression of activating receptors involved in NK‐cell‐mediated target cell killing without affecting ADCC

et al. 2013

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In certain infection sites or tumor tissues, the disruption of homeostasis can give rise to a hypoxic microenvironment, which, in turn, can alter the function of different immune cell types and favor the progression of the disease. Natural killer (NK) cells are directly involved in the elimination of virus-infected or transformed cells, however it is unknownwhether their function is affected by hypoxia or not. In this study, we show that NK cells adapt to a hypoxic environment by upregulating the hypoxia-inducible factor 1α. However, NK cells lose their ability to upregulate the surface expression of the major activating NK-cell receptors (NKp46, NKp30, NKp44, and NKG2D) in response to IL-2 (or other activating cytokines, including IL-15, IL-12, and IL-21). These altered phenotypic features correlate with reduced responses to triggering signals resulting in impaired capability of killing infected or tumor target cells. Remarkably, hypoxia does not significantly alter the surface density and the triggering function of the Fc-γ receptor CD16, thus allowing NK cells to maintain their capability of killing target cells via antibody-dependent cellular cytotoxicity. This finding offers an important clue for exploitation of NK cell in antibody-based immunotherapy of cancer. Keywords: ADCC · Hypoxia · NK cells · Tumor Escape · Tumor MicroenvironmentAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionAs a component of innate immunity, natural killer (NK) cells play an important role in the control of virus infections and in cancer immune surveillance [1][2][3][4][5]. They can kill a wide range of cells that, Correspondence: Prof. Lorenzo Moretta e-mail: lorenzomoretta@ospedale-gaslini.ge.it upon neoplastic transformation or virus infection, have downregulated major histocompatibility complex class I surface expression.To recognize their targets, NK cells use a complex array of activating receptors and/or coreceptors. These mainly include the natural cytotoxicity receptors (NCRs, i.e. NKp46, NKp30, and * These authors contributed equally to this work. * * These authors share senior authorship. [5,[11][12][13][14], there are still many obstacles for the effective use of these cells in immunotherapy. Both tumors and viruses have developed different escape mechanisms to avoid NK-cell immunosurveillance. For example, certain viruses can shape the expression profile of various NK-receptor ligands in infected cells [15]. Similarly, tumor cells may shed from the surface certain NKG2D ligands thus avoiding NK-cell-mediated attack [16]. In addition, several lines of evidence indicate that the tumor microenvironment may impact the real ability of NK cells to clear pathologic cells [17][18][19][20][21][22]. Indeed, while cytokines such as IL-2, IL-15, IL-12, and IL-21 can enhance NK-cell function, other factors induced at the tumor site, such as IDO, PGE 2 , and TGF-β, or even the direct interaction with tumor cells or tumor-associated stromal cells, may impai...

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“…+ lymphocytes although the expression pattern of NK cells includes variety of receptors including killer immunoglobulin-like receptors (KIR) [38], CD16 (Fcγ-receptor III), which mediates antibody-dependent cellular cytotoxity [25,32], natural killer group (NKG) receptors, cytotoxic receptors NKp30, NKp44, NKp46 [20]. NK cells differentiation and development is connected with the consequent change of repertoire of receptors present in the cell and their acquisition of functional properties.…”

Section: Cd56mentioning

confidence: 99%

“…In decidua oxygen, partial pressure at the beginning of pregnancy constitutes 50 mm of mercury (8%) and in the end of the first trimester it increases up to 70 mm of mercury (12%), in proximity of spiral arteries it reaches 90-100 mm of mercury (20%) [36]. In the experiments with NK cells obtained in vitro from human hematopoietic stem cells, it was detected that in hypoxic conditions (1% O 2 ) NK cells decrease expression of NKp30 and NKG2D activation markers [38]. At 10% О 2 decidual NK cells restore expression of NKG2D receptor, and at 21% О 2 decidual NK cells reduce CD56 expression compared to culturing conditions at 10% О 2 [36].…”

Section: Oxygen Supply Modifiers Nk Cells Differentiation At Pregnancymentioning

confidence: 99%

PECULIARITIES OF NK CELLS DIFFERENTIATION: CD56dim AND CD56bright NK CELLS AT PREGNANCY AND IN NON-PREGNANT STATE

Михайлова¹,

Белякова²,

Selkov³

et al. 2017

Med. immunol.

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Oxygen tension regulates NK cells differentiation from hematopoietic stem cells in vitro

Cited by 12 publications

References 40 publications

Monocytes inhibit NK activityviaTGF-β in patients with obstructive sleep apnoea

Monocytes inhibit NK activityviaTGF-β in patients with obstructive sleep apnoea

Hypoxia downregulates the expression of activating receptors involved in NK‐cell‐mediated target cell killing without affecting ADCC

PECULIARITIES OF NK CELLS DIFFERENTIATION: CD56dim AND CD56bright NK CELLS AT PREGNANCY AND IN NON-PREGNANT STATE

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