Analyses of phenotypic and functional characteristics of CX3CR1‐expressing natural killer cells

Hamann, Isabell; Unterwalder, Nadine; Cardona, Astrid E.; Meisel, Christian; Zipp, Frauke; Ransohoff, Richard M.; Infante-Duarte, Carmen

doi:10.1111/j.1365-2567.2011.03409.x

Cited by 81 publications

(79 citation statements)

References 46 publications

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“…6 CX 3 CR1 is furthermore expressed by macrophage/ dendritic cell precursors, 7 various dendritic cell (DC) progenitors, a nonclassic CD8␣ ϩ DC subset, 8 and plasmacytoid DCs. Aside from the prominent expression in the mononuclear myeloid compartment, CX 3 CR1 receptor expression has been reported for an NK cell subset 3,9 and certain T-cell populations. 3,10,11 The in vivo expression pattern of the ligand CX 3 CL1 remains less well defined and controversial 12 but has been reported for neurons, 13 intestinal epithelium, 14 and inflamed endothelium.…”

Section: Introductionmentioning

confidence: 99%

In vivo structure/function and expression analysis of the CX3C chemokine fractalkine

Kim

Vallon-Eberhard

Zigmond

et al. 2011

Blood

233

223

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The CX 3 C chemokine family is composed of only one member, CX 3 CL1, also known as fractalkine, which in mice is the sole ligand of the G proteincoupled, 7-transmembrane receptor CX 3 CR1. Unlike classic small peptide chemokines, CX 3 CL1 is synthesized as a membrane-anchored protein that can promote integrin-independent adhesion. Subsequent cleavage by metalloproteases, either constitutive or induced, can generate shed CX 3 CL1 entities that potentially have chemoattractive activity. To study the CX 3 C interface in tissues of live animals, we generated transgenic mice (CX 3 CL1 cherry :CX 3 CR1 gfp ), which express red and green fluorescent reporter genes under the respective control of the CX 3 CL1 and CX 3 CR1 promoters. Furthermore, we performed a structure/function analysis to differentiate the in vivo functions of membranetethered versus shed CX 3 CL1 moieties by comparing their respective ability to correct established defects in macrophage function and leukocyte survival in IntroductionChemokine (CX 3 C motif) ligand 1 (CX 3 CL1), also known as fractalkine or neurotactin, 1,2 and its receptor CX 3 CR1 3 have been assigned their own CX 3 C chemokine family. This classification is based on the 3 amino acid gap between its N-terminal cysteines in CX 3 CL1, with no spacing in CC chemokines and only one intervening amino acid in CXC chemokines. 4 CX 3 CL1 is furthermore structurally unique in that it is synthesized as a type I transmembrane protein with the CX 3 C chemokine domain presented on an extended stalk. 1,2 Both CX 3 CL1 and CX 3 CR1 are widely expressed throughout the organism; but in given tissues, expression is often highly cell type-specific. Taking advantage of mice that harbor a targeted replacement of the CX 3 CR1 gene by a GFP reporter, 5 we could, for instance, show that CX 3 CR1 expression in the brain is restricted to microglia. CX 3 CR1 expression in the gut was found limited to lamina propria macrophages and CX 3 CR1 expression in the blood is largely restricted to monocytes, which are uniform CX 3 CR1 positive, albeit with discrete expression levels. 6 CX 3 CR1 is furthermore expressed by macrophage/ dendritic cell precursors, 7 various dendritic cell (DC) progenitors, a nonclassic CD8␣ ϩ DC subset, 8 and plasmacytoid DCs. Aside from the prominent expression in the mononuclear myeloid compartment, CX 3 CR1 receptor expression has been reported for an NK cell subset 3,9 and certain T-cell populations. 3,10,11 The in vivo expression pattern of the ligand CX 3 CL1 remains less well defined and controversial 12 but has been reported for neurons, 13 intestinal epithelium, 14 and inflamed endothelium. 2 Notably, in humans eotaxin-3/CC chemokine ligand 26 was recently reported to be a functional ligand for CX 3 CR1 15 ; in mice, the CCL26 gene, however, is a pseudogene.The analysis of CX 3 C receptor and ligand knockout mice 5,16 has revealed a number of phenotypes resulting from the lack of CX 3 CR1/ CX 3 CL1 interactions. [17][18][19][20] However, in-depth knowledge of the physiologic rol...

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Section: Introductionmentioning

confidence: 99%

In vivo structure/function and expression analysis of the CX3C chemokine fractalkine

Kim

Vallon-Eberhard

Zigmond

et al. 2011

Blood

233

223

View full text Add to dashboard Cite

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“…More recently, further markers were shown to distinguish between different maturation subsets. We showed that CX3CR1 − NK cells were immature NK cells and that the chemokine receptor CX3CR1 may serve in combination with CD56, CD57, CD62L, and CD27 to define different steps of NK cell maturation (Hamann et al, 2011). The NK cell maturation and receptor expression profile is depicted in Figure 1.…”

Section: Introductionmentioning

confidence: 99%

The Role of Natural Killer Cells in Multiple Sclerosis and Their Therapeutic Implications

Chanvillard¹,

Jacolik²,

Infante-Duarte³

et al. 2013

Front. Immunol.

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Multiple sclerosis (MS) is assumed to be an autoimmune disease initiated by autoreactive T cells that recognize central nervous system antigens. Although adaptive immunity is clearly involved in MS pathogenesis, innate immunity increasingly appears to be implicated in the disease. We and others have presented evidence that natural killer (NK) cells may be involved in immunoregulation in MS, leading to the question of whether a particular NK cell subtype will account for this effect. Changes of NK cell functionality in MS were associated with MS activity, and depletion of NK cells exacerbated the course of disease in a murine model of MS, experimental autoimmune encephalomyelitis. Several studies described a deficiency and transient “valleys” in NK cell killing activity in human MS, which may coincide with symptomatic relapse. However, the molecular basis of the defect in killing activity has not been determined. We discuss results on the expression of perforin in CD16+ NK cells and the existence of an inverse relationship between myelin loaded phagocytes and the proportion of CD16+ NK cells expressing perforin in the circulation. This inverse relationship is consistent with a role for NK cell killing activity in dampening autoimmunity. On the other hand, it has been broadly reported that first line MS therapies, such as interferon-beta, glatiramer acetate as well as escalation therapies such as fingolimod, daclizumab, or mitoxantrone seem to affect NK cell functionality and phenotype in vivo. Therefore, in this review we consider evidence for the immunoregulatory role of NK cells in MS and its animal models. Furthermore, we discuss the effect of MS treatments on NK cell activity.

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“…Interestingly, a reduction of blood NK cells expressing CX3CR1 correlated with disease severity (54). Because CD56 bright NK cells were shown to be CX3CR1 2 in normal donors, it would be interesting to further look at the capacity of daclizumab to modulate CX3CR1 expression on NK cell subtypes (58). Manipulation of NK cells in animal models of EAE leads to contradictory results.…”

Section: Nk Cell Modifications Associated With Cns Disordersmentioning

confidence: 99%

NK Cells in Central Nervous System Disorders

Poli

Kmiecik

Domingues

et al. 2013

The Journal of Immunology

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NK cells are important players in immunity against pathogens and neoplasms. As a component of the innate immune system, they are one of the first effectors on sites of inflammation. Through their cytokine production capacities, NK cells participate in the development of a potent adaptive immune response. Furthermore, NK cells were found to have regulatory functions to limit and prevent autoimmunity via killing of autologous immune cells. These paradoxical functions of NK cells are reflected in CNS disorders. In this review, we discuss the phenotypes and functional features of peripheral and brain NK cells in brain tumors and infections, neurodegenerative diseases, acute vascular and traumatic damage, as well as mental disorders. We also discuss the implication of NK cells in neurotoxicity and neuroprotection following CNS pathology, as well as the crosstalk between NK cells and brain-resident immune cells.

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Analyses of phenotypic and functional characteristics of CX3CR1‐expressing natural killer cells

Cited by 81 publications

References 46 publications

In vivo structure/function and expression analysis of the CX3C chemokine fractalkine

In vivo structure/function and expression analysis of the CX3C chemokine fractalkine

The Role of Natural Killer Cells in Multiple Sclerosis and Their Therapeutic Implications

NK Cells in Central Nervous System Disorders

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