Evidence for NK Cell Subsets Based on Chemokine Receptor Expression

Berahovich, Robert; Lai, Nu L.; Zheng, Wei; Lanier, Lewis L.; Schall, Thomas J.

doi:10.4049/jimmunol.177.11.7833

Cited by 171 publications

(145 citation statements)

References 20 publications

(14 reference statements)

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“…DC maturation induced by IFN-g/FMKp led to an enhanced (41.5-fold increase in chemiluminescence) secretion of eleven chemokines as compared with TNF-a/PGE2-induced maturation. These chemokines included CCL5, CXCL10 and CCL19 to which NK cells can respond [23][24][25]. Quantification with ELISA confirmed that these chemokines were indeed produced by IFN-g/FMKp-matured DC and not by TNF-a/PGE2-matured DC (Fig.…”

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confidence: 73%

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Klebsiella pneumoniae‐triggered DC recruit human NK cells in a CCR5‐dependent manner leading to increased CCL19‐responsiveness and activation of NK cells

et al. 2010

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Besides their role in destruction of altered self-cells, NK cells have been shown to potentiate T-cell responses by interacting with DC. To take advantage of NK-DC crosstalk in therapeutic DC-based vaccination for infectious diseases and cancer, it is essential to understand the biology of this crosstalk. We aimed to elucidate the in vitro mechanisms responsible for NK-cell recruitment and activation by DC during infection. To mimic bacterial infection, DC were exposed to a membrane fraction of Klebsiella pneumoniae, which triggers TLR2/4. DC matured with these bacterial fragments can actively recruit NK cells in a CCR5-dependent manner. An additional mechanism of DC-induced NK-cell recruitment is characterized by the induction of CCR7 expression on CD56 dim CD16 1 NK cells after physical contact with membrane fraction of K. pneumoniae-matured DC, resulting in an enhanced migratory responsiveness to the lymph node-associated chemokine CCL19. Bacterial fragment-matured DC do not only mediate NK-cell migration but also meet the prerequisites needed for augmentation of NK-cell cytotoxicity and IFN-c production, the latter of which contributes to Th1 polarization.Key words: CCR5 . CCR7 . NK-DC interaction . Th1 polarization Supporting Information available online Introduction NK cells are important effector cells in the innate immune response against virally infected or malignantly transformed cells and their cytotoxicity is regulated by a delicate balance of inhibitory and activating signals [1]. Recent studies suggest that the interplay between NK cells and DC, the specialized antigenpresenting cell of the innate immune system [2], is critical in shaping the adaptive immune response [3]. This concept originates from several lines of evidence including: the discovery of NK cells colocalizing with DC in the T-cell areas of lymph nodes [4,5], the coupling of NK-cell recruitment to lymph nodes Ã These authors contributed equally to this work. 3138with the induction of more potent Th1 skewing [3], and the identification of NK-cell subpopulations with helper properties [6]. Although the exact mechanisms of NK-DC interaction remain to be elucidated, increasing evidence supports the importance of bidirectional NK-DC crosstalk [7,8].On the one hand, NK-DC crosstalk is characterized by the capacity of activated NK cells to induce DC maturation with elevated IL-12p70 production and subsequently an increased capacity to induce Th1 and CTL responses [9]. This NK-induced DC maturation depends at least in part on soluble factors such as and as well as on engagement of the natural cytotoxicity triggering receptor 30 [12]. Moreover, NK cells control the quality of the adaptive immune response by natural cytotoxicity triggering receptor 30-mediated lysis of immature or inadequately matured DC [13], enabling only fully mature DC to migrate into lymph nodes and subsequently prime T cells. On the other hand, DC are able to induce NK-cell proliferation, augmentation of cytotoxicity and cytokine secretion [8]. The DC-induced modulati...

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confidence: 73%

“…In steady-state conditions, the CD56 bright CD16 À NK-cell subpopulation has been reported to express CCR7 [25], which allows them to migrate into lymph nodes [26]. However, in response to IL-18-producing monocytes, induction of CCR7 has also been observed on CD56 dim CD16 1 NK cells [6].…”

Section: Dc-dependent Induction Of Ccr7 Expression On Nk Cellsmentioning

confidence: 99%

Klebsiella pneumoniae‐triggered DC recruit human NK cells in a CCR5‐dependent manner leading to increased CCL19‐responsiveness and activation of NK cells

et al. 2010

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“…Intestinal epithelial cell lines, IEC6 (rat, passage 36-46) and CaCo-2 (human, passage [30][31][32][33][34][35][36][37][38][39][40], were grown on Lab-Tek I chamber slides and stained for CXCR3 as described above. To localize CXCR3 expression in intestinal tissues, 4-µm sections were prepared, and laser capture microdissection (mouse tissue) or immunohistochemistry (human tissue) were performed as previously described.…”

Section: Cxcr3 Expression In Intestinal Cell Lines and Tissuesmentioning

confidence: 99%

Gliadin Induces an Increase in Intestinal Permeability and Zonulin Release by Binding to the Chemokine Receptor CXCR3

et al. 2008

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Background & Aims-Celiac disease is an immune-mediated enteropathy triggered by gliadin, a component of the grain protein gluten. Gliadin induces an MyD88-dependent zonulin release that leads to increased intestinal permeability, a postulated early element in the pathogenesis of celiac disease. We aimed to establish the molecular basis of gliadin interaction with intestinal mucosa leading to intestinal barrier impairment.

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“…CD56 bright NK cells preferentially accumulate in the T cell area of the lymph node, presumably through their selective expression of CCR7 and CD62L (4,5). The developmental relationship between CD56 dim and CD56 bright NK cells is not clear, and these two subpopulations of NK cells may represent two developmentally distinct subsets.…”

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confidence: 99%

The CD16−CD56bright NK Cell Subset Is Resistant to Reactive Oxygen Species Produced by Activated Granulocytes and Has Higher Antioxidative Capacity Than the CD16+CD56dim Subset

Harlin

Hanson

Johansson

et al. 2007

The Journal of Immunology

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Human NK cells can be divided into CD56dim and CD56bright subsets. These two types of NK cells respond to different types of stimuli, with CD56dim NK cells having direct cytotoxic ability and CD56bright NK cells having mainly an immunoregulatory function. We show that the CD16+CD56dim NK subset is characterized by sensitivity to cell death induced by activated granulocytes. We identified hydrogen peroxide (H2O2) as the major effector molecule responsible for the cytotoxic effect of granulocytes on CD56dim NK cells, because the ability of granulocytes to kill CD56dim NK cells was completely abrogated in the presence of the hydrogen peroxide scavenger catalase. When exposing NK cells to H2O2, CD56dim cells showed rapid mitochondrial depolarization and down-regulation of activating NKRs, eventually resulting in cell death, whereas CD56bright cells remained unaffected. The difference in sensitivity to H2O2 was mirrored by a difference in intracellular oxidation levels between CD56dim and CD56bright NK cells, and cell lysates from the latter subset possessed a greater ability to block H2O2-mediated oxidation. Our data may explain the preferential accumulation of CD56bright NK cells often seen in environments rich in reactive oxygen species, such as at sites of chronic inflammation and in tumors.

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Evidence for NK Cell Subsets Based on Chemokine Receptor Expression

Cited by 171 publications

References 20 publications

Klebsiella pneumoniae‐triggered DC recruit human NK cells in a CCR5‐dependent manner leading to increased CCL19‐responsiveness and activation of NK cells

Klebsiella pneumoniae‐triggered DC recruit human NK cells in a CCR5‐dependent manner leading to increased CCL19‐responsiveness and activation of NK cells

Gliadin Induces an Increase in Intestinal Permeability and Zonulin Release by Binding to the Chemokine Receptor CXCR3

The CD16−CD56bright NK Cell Subset Is Resistant to Reactive Oxygen Species Produced by Activated Granulocytes and Has Higher Antioxidative Capacity Than the CD16+CD56dim Subset

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