NK-DC Crosstalk in Immunity to Microbial Infection

Thomas, Richard K.; Yang, Xi

doi:10.1155/2016/6374379

Cited by 57 publications

(64 citation statements)

References 63 publications

(65 reference statements)

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“…The expression of NKG2A, an inhibitory member of the NKG2 receptor family that binds to HLA-E, was observed to be decreased in CD patients. The receptor is expressed on developing NK cells before the expression of KIR [3,10,11]. Its decreased expression may contribute towards a reduced activating threshold of NK cells in CD patients.…”

Section: Discussionmentioning

confidence: 99%

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Phenotypic and Functional Changes in Peripheral Blood Natural Killer Cells in Crohn Disease Patients

Samarani

Sagala

Jantchou

et al. 2020

Mediators of Inflammation

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We investigated activation status, cytotoxic potential, and gut homing ability of the peripheral blood Natural Killer (NK) cells in Crohn disease (CD) patients. For this purpose, we compared the expression of different activating and inhibitory receptors (KIR and non-KIR) and integrins on NK cells as well as their recent degranulation history between the patients and age-matched healthy controls. The study was conducted using freshly obtained peripheral blood samples from the study participants. Multiple color flow cytometry was used for these determinations. Our results show that NK cells from treatment-naïve CD patients expressed higher levels of activating KIR as well as other non-KIR activating receptors vis-à-vis healthy controls. They also showed increased frequencies of the cells expressing these receptors. The expression of several KIR and non-KIR inhibitory receptors tended to decrease compared with the cells from healthy donors. NK cells from the patients also expressed increased levels of different gut-homing integrin molecules and showed a history of increased recent degranulation events both constitutively and in response to their in vitro stimulation. Furthermore, treatment of the patients tended to reverse these NK cell changes. Our results demonstrate unequivocally, for the first time, that peripheral blood NK cells in treatment-naïve CD patients are more activated and are more poised to migrate to the gut compared to their counterpart cells from healthy individuals. Moreover, they show that treatment of the patients tends to normalize their NK cells. The results suggest that NK cells are very likely to play a role in the immunopathogenesis of Crohn disease.

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Section: Discussionmentioning

confidence: 99%

“…By secreting these soluble mediators, NK cells can affect the quality and strength of an adaptive immune response. They can also modulate adaptive immune responses by their interactions with dendritic cells (DC), effector T cells, and Tregs [9,10].…”

Section: Introductionmentioning

confidence: 99%

Phenotypic and Functional Changes in Peripheral Blood Natural Killer Cells in Crohn Disease Patients

Samarani

Sagala

Jantchou

et al. 2020

Mediators of Inflammation

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“…The importance of NK-DC crosstalk in regulating immune responses in infections and immunotherapy has been well established [12,20,21]. Advances in intravital imaging of T cells and NK cells in lymph nodes revealed interesting dynamic migration behaviors that involve structural and chemical cues in promoting effective cell-cell interactions in vivo [22,23].…”

Section: Discussionmentioning

confidence: 99%

A New Microfluidic Platform for Studying Natural Killer Cell and Dendritic Cell Interactions

et al. 2019

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The importance of the bi-directional natural killer–dendritic cell crosstalk in coordinating anti-tumour and anti-microbial responses in vivo has been well established. However, physical parameters associated with natural killer–dendritic cell interactions have not been fully elucidated. We have previously used a simple “Y” shaped microfluidic device to study natural killer cell-migratory responses toward chemical gradients from a conditioned medium of dendritic cells. There are, however, limitations of the Y-shaped microfluidic devices that could not support higher throughput analyses and studies of cell–cell interactions. Here, we report two novel microfluidic devices (D3-Chip, T2-Chip) we applied in advanced studies of natural killer-cell migrations and their interactions with dendritic cells in vitro. The D3-Chip is an improved version of the previously published Y-shaped device that supports high-throughput analyses and docking of the cells of interest in the migration assay before they are exposed to a chemical gradient. The T2-Chip is created to support analyses of natural killer–dendritic cell cell–cell interactions without the requirement of promoting a natural killer cell to migrate long distances to find a loaded dendritic cell in the device. Using these two microfluidic platforms, we observe quantitative differences in the abilities of the immature and lipopolysaccharide-activated mature dendritic cells to interact with activated natural killer cells. The contact time between the activated natural killer cells and immature dendritic cells is significantly longer than that of the mature dendritic cells. There is a significantly higher frequency of an immature dendritic cell coming into contact with multiple natural killer cells and/or making multiple simultaneous contacts with multiple natural killer cells. To contrast, an activated natural killer cell has a significantly higher frequency of coming into contact with the mature dendritic cells than immature dendritic cells. Collectively, these differences in natural killer–dendritic cell interactions may underlie the differential maturation of immature dendritic cells by activated natural killer cells. Further applications of these microfluidic devices in studying natural killer–dendritic cell crosstalk under defined microenvironments shall enrich our understanding of the functional regulations of natural killer cells and dendritic cells in the natural killer–dendritic cell crosstalk.

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“…Cross-talk between NK cells and DCs is believed to play a major role during immune responses ( 12 ), and activated, but not resting, DCs have been shown to express NKG2D ligands ( 13 – 17 ). Several studies in mice and humans have reported NKG2D ligand expression on DCs stimulated with cytokines ( 18 ) or infected with pathogens ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

Chronic In Vivo Interaction of Dendritic Cells Expressing the Ligand Rae-1ε with NK Cells Impacts NKG2D Expression and Function

et al. 2017

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To investigate how dendritic cells (DCs) interact with NK cells in vivo, we developed a novel mouse model in which Rae-1ε, a ligand of the NKG2D receptor, is expressed in cells with high levels of CD11c. In these CD11c-Rae1 mice, expression of Rae-1 was confirmed on all subsets of DCs and a small subset of B and T cells, but not on NK cells. DC numbers and activation status were unchanged, and NK cells in these CD11c-Rae1 mice presented the same Ly49 repertoire and maturation levels as their littermate wildtype controls. Early NK cell activation after mouse CMV infection was slightly lower than in wildtype mice, but NK cell expansion and viral control were comparable. Notably, we demonstrate that chronic interaction of NK cells with NKG2D ligand–expressing DCs leads to a reversible NKG2D down-modulation, as well as impaired NKG2D-dependent NK cell functions, including tumor rejection. In addition to generating a useful mouse model, our studies reveal in vivo the functional importance of the NK cell and DC cross-talk.

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NK-DC Crosstalk in Immunity to Microbial Infection

Cited by 57 publications

References 63 publications

Phenotypic and Functional Changes in Peripheral Blood Natural Killer Cells in Crohn Disease Patients

Phenotypic and Functional Changes in Peripheral Blood Natural Killer Cells in Crohn Disease Patients

A New Microfluidic Platform for Studying Natural Killer Cell and Dendritic Cell Interactions

Chronic In Vivo Interaction of Dendritic Cells Expressing the Ligand Rae-1ε with NK Cells Impacts NKG2D Expression and Function

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