Coexpression of CD58 or CD48 with Intercellular Adhesion Molecule 1 on Target Cells Enhances Adhesion of Resting NK Cells

Barber, Domingo F.; Long, Eric O.

doi:10.4049/jimmunol.170.1.294

Cited by 91 publications

(114 citation statements)

References 24 publications

Supporting

Mentioning

110

Contrasting

Unclassified

Order By: Relevance

“…After isolation, cells were cultured under the indicated conditions for migration, conjugation (65)(66)(67), lentivirus transfection, and viability assays as described.…”

Section: Methodsmentioning

confidence: 99%

Acetylcholine-producing NK cells attenuate CNS inflammation via modulation of infiltrating monocytes/macrophages

Jiang

Han

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The nonneural cholinergic system of immune cells is pivotal for the maintenance of immunological homeostasis. Here we demonstrate the expression of choline acetyltransferase (ChAT) and cholinergic enzymes in murine natural killer (NK) cells. Ly6Chi monocytes directly via the disruption of tolerance and inhibited the production of proinflammatory cytokines. Interestingly, ChAT + NK cells and CCR2 + Ly6C hi monocytes formed immune synapses; moreover, the impact of ChAT + NK cells was mediated by α7-nicotinic acetylcholine receptors. Finally, the NK cell cholinergic system up-regulated in response to autoimmune activation in multiple sclerosis, perhaps reflecting the severity of disease. Therefore, this study extends our understanding of the nonneural cholinergic system and the protective immune effect of acetylcholine-producing NK cells in autoimmune diseases.

show abstract

“…After isolation, cells were cultured under the indicated conditions for migration, conjugation (65)(66)(67), lentivirus transfection, and viability assays as described.…”

Section: Methodsmentioning

confidence: 99%

Acetylcholine-producing NK cells attenuate CNS inflammation via modulation of infiltrating monocytes/macrophages

Jiang

Han

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…The b2-integrin LFA-1 plays a pivotal role in NK-cell conjugate formation. Engagement of its ligand ICAM-1 is sufficient for the formation of stable effector-target conjugates [4]. Moreover, LFA-1 signals are important for granule polarization in NK cells [5].…”

mentioning

confidence: 99%

Statins inhibit NK‐cell cytotoxicity by interfering with LFA‐1‐mediated conjugate formation

2009

View full text Add to dashboard Cite

Inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A reductase, commonly referred to as statins, are inhibitors of cholesterol biosynthesis. They are broadly used for treating hypercholesterolemia and for prevention of cardio-and cerebrovascular diseases. Recent publications show that statins also act as immunomodulatory drugs. Here, we show that lipophilic statins inhibit NK-cell degranulation and cytotoxicity. This effect was reversible by addition of substrates of isoprenylation, but not by addition of cholesterol. In NK-target cell conjugates intracellular Ca 21 flux was unaffected by statin treatment. However, statins strongly reduced the amount of conjugate formation between NK and target cells. This inhibition was paralleled by a statin-dependent inhibition of LFA-1-mediated adhesion and a reduction of NK-cell polarization. This demonstrates that statins impair the formation of effector-target cell conjugates resulting in the disruption of early signaling and the loss of NK-cell cytotoxicity.Key words: Adhesion molecules . Cytotoxicity . Human . NK cells IntroductionNK cells belong to the innate arm of the immune system and are important for an early immune response against viral infections and against tumor formation [1]. They are able to detect and selectively kill potentially dangerous cells. Furthermore, they can secrete cytokines and thereby mediate the communication between the innate and adaptive parts of an immune response. Specific killing of infected and transformed cells depends on several discrete steps that lead to polarization and exocytosis of lytic granules towards the target cell [2,3]. As a very first step the contact between NK cells and potential targets is established. Different NK-cell receptors and adhesion molecules mediate this event. LFA-1 plays a special role in the complete process of NK-cell activation. Engagement of LFA-1 by its ligand ICAM-1 on target cells is the central step in the stable adhesion of NK cells to their target cells and is sufficient to induce the polarization of lytic granules in resting NK cells [4,5]. NK-cell cytotoxicity is achieved by degranulation of these accumulated granules in the direction of the target. For this, mobilization of Ca 21 from intracellular stores is needed, which is mediated by the activation of the phospholipase C-g (PLCg) and PKC signaling pathways [6]. Inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, commonly referred to as statins, are potent inhibitors of cholesterol biosynthesis. They mimic HMGCoA and thereby block the active site of this essential enzyme [7]. Statins are broadly used as a pharmacologic therapy for treating hypercholesterolemia and for prevention of cardio-and cerebrovascular diseases [8]. Accumulating evidence occurs that statins also act as immunomodulatory drugs [9][10][11]. In various experimental settings they were shown to affect different kinds of immune cells including T cells [12,13], B cells [14] and antigenpresenting cells [13]. Also, the function of NK cells can be inh...

show abstract

“…In fact, resting human ex vivo NK cells appear to require engagement of at least two independent receptors to become activated (37). These same investigators also demonstrated that when LFA-3 or CD48, ligands for CD2 and 2B4, respectively, are coexpressed on target cells with ICAM-1, a ligand for LFA-1, this led to enhanced adhesion of resting NK cells, significantly beyond that observed to target cells expressing only ICAM-1 (38). Furthermore, in the case of LFA-1 expressed on human NK cells, it also can physically associate with DNAM-1, another adhesion and signaling receptor and regulate its phosphorylation state and ability to induce NK cell cytotoxicity (39).…”

Section: Discussionmentioning

confidence: 90%

“…Human NK cells can bind ICAM-1 directly with no direct stimulus, albeit to a much lesser extent for resting human NK cells, therefore it has been proposed that NK cells may be unique (38), and unlike T cells, in not requiring stimulation through an independent activating receptor before LFA-1 can bind tightly to ICAM-1. We did not observe significant binding of resting mouse NK cells or the rat RNK-16 cell to ICAM-1 in the absence of stimulation via an activating receptor.…”

Section: Discussionmentioning

confidence: 99%

Activating Ly-49 Receptors Regulate LFA-1-Mediated Adhesion by NK Cells

Osman

Burshtyn

Kane

2007

The Journal of Immunology

View full text Add to dashboard Cite

NK cells are important for innate resistance to tumors and viruses. Engagement of activating Ly-49 receptors expressed by NK cells leads to rapid NK cell activation resulting in target cell lysis and cytokine production. The ITAM-containing DAP12 adapter protein stably associates with activating Ly-49 receptors, and couples receptor recognition with generation of NK responses. Activating Ly-49s are potent stimulators of murine NK cell functions, yet how they mediate such activities is not well understood. We demonstrate that these receptors trigger LFA-1-dependent tight conjugation between NK cells and target cells. Furthermore, we show that activating Ly-49 receptor engagement leads to rapid DAP12-dependent up-regulation of NK cell LFA-1 adhesiveness to ICAM-1 that is also dependent on tyrosine kinases of the Syk and Src families. These results indicate for the first time that activating Ly-49s control adhesive properties of LFA-1, and by DAP12-dependent inside-out signaling. Ly-49-driven mobilization of LFA-1 adhesive function may represent a fundamental proximal event during NK cell interactions with target cells involving activating Ly-49 receptors, leading to target cell death.

show abstract

Coexpression of CD58 or CD48 with Intercellular Adhesion Molecule 1 on Target Cells Enhances Adhesion of Resting NK Cells

Cited by 91 publications

References 24 publications

Acetylcholine-producing NK cells attenuate CNS inflammation via modulation of infiltrating monocytes/macrophages

Acetylcholine-producing NK cells attenuate CNS inflammation via modulation of infiltrating monocytes/macrophages

Statins inhibit NK‐cell cytotoxicity by interfering with LFA‐1‐mediated conjugate formation

Activating Ly-49 Receptors Regulate LFA-1-Mediated Adhesion by NK Cells

Contact Info

Product

Resources

About