Potassium channels K<sub>v</sub>1.3 and K<sub>v</sub>1.5 are expressed on blood‐derived dendritic cells in the central nervous system

Mullen, Katherine M.; Rózycka, M; Rus, Horea; Hu, Lina; Cudrici, Cornelia; Zafranskaia, Ekaterina; Pennington, Michael W.; Johns, David C.; Judge, Susan I.V.; Calabresi, Peter A.

doi:10.1002/ana.20884

Cited by 57 publications

(59 citation statements)

References 44 publications

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“…Similar data showing interaction between immature DCs with T cells have been reported in MS plaques (Mullen et al, 2006) in which DCs were found to express co-stimulatory molecule CD86 and to interact with CD8 cells (Mullen et al, 2006;Serafini et al, 2006). Immature DCs in NLGM were also found by us to engulf myelin antigens in agreement with their function in antigen processing and presentation (Reis e Sousa, 2006).…”

Section: Discussionsupporting

confidence: 80%

Dendritic cells are abundant in non-lesional gray matter in multiple sclerosis

Cudrici

Ito

Zafranskaia

et al. 2007

Experimental and Molecular Pathology

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We have analyzed the localization of dendritic cells (DCs) in non-lesional gray matter (NLGM) in comparison to non-lesional white matter (NLWM) and acute or chronic active multiple sclerosis (MS) lesions. Immunohistochemistry was performed on cryostat sections for DCs markers (CD209, CD205, CD83) and other markers for inflammatory cells (CD68, CD8, CD4, CD3, CCR7, CCR5). We found cells expressing CD209 and containing myelin basic protein in both perivascular and parenchymal areas of NLGM. Our findings showing the expression of CD209 + cells in NLGM parenchymal areas are surprising relative to the previous literature which reported the presence of CD209 + DCs only in MS plaque perivascular areas. Although less numerous than CD209 + cells, NLGM cells expressing mature DCs marker CD205 were consistently detected in perivascular cuffs of most lesions. In double labeling experiments, some but not all of the CD209 + cells also expressed CD68 and CCR5. We also found CD209 + cells in close contact with CD3 + lymphocytes suggesting that DCs might contribute to the local activation of pathogenic T cells in the NLGM. Since injury to the NLGM is one of the key factors associated with disability accumulation, targeting DCs may represent a possible new therapeutic approach in MS to prevent disease progression.

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Section: Discussionsupporting

confidence: 80%

Dendritic cells are abundant in non-lesional gray matter in multiple sclerosis

Cudrici

Ito

Zafranskaia

et al. 2007

Experimental and Molecular Pathology

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“…DCs are known to express voltage-gated K ϩ channels belonging to the Shaker (Kv1) family, presumably Kv1.3 and Kv1.5 (13,14). Accordingly, margatoxin (MgTx, 0.1 nM) and ICAGEN-4 (10 M, Ref.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, DCs were shown to contain voltage-gated K ϩ (Kv) channels, belonging to Kv1 channel family, which are up-regulated by LPS stimulation and play a role in cytokine production (13,14). In the present study, we address the question whether Kv channels can modulate Ca 2ϩ entry in DCs by maintaining the electrochemical driving force for Ca 2ϩ influx (15) and thus participate in Ca 2ϩ -dependent DC functions.…”

Section: Endritic Cells (Dcs)mentioning

confidence: 98%

Ion Channels Modulating Mouse Dendritic Cell Functions

Matzner

Zemtsova

Xuân

et al. 2008

The Journal of Immunology

105

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Ca2+-mediated signal transduction pathways play a central regulatory role in dendritic cell (DC) responses to diverse Ags. However, the mechanisms leading to increased [Ca2+]i upon DC activation remained ill-defined. In the present study, LPS treatment (100 ng/ml) of mouse DCs resulted in a rapid increase in [Ca2+]i, which was due to Ca2+ release from intracellular stores and influx of extracellular Ca2+ across the cell membrane. In whole-cell voltage-clamp experiments, LPS-induced currents exhibited properties similar to the currents through the Ca2+ release-activated Ca2+ channels (CRAC). These currents were highly selective for Ca2+, exhibited a prominent inward rectification of the current-voltage relationship, and showed an anomalous mole fraction and a fast Ca2+-dependent inactivation. In addition, the LPS-induced increase of [Ca2+]i was sensitive to margatoxin and ICAGEN-4, both inhibitors of voltage-gated K+ (Kv) channels Kv1.3 and Kv1.5, respectively. MHC class II expression, CCL21-dependent migration, and TNF-α and IL-6 production decreased, whereas phagocytic capacity increased in LPS-stimulated DCs in the presence of both Kv channel inhibitors as well as the ICRAC inhibitor SKF-96365. Taken together, our results demonstrate that Ca2+ influx in LPS-stimulated DCs occurs via Ca2+ release-activated Ca2+ channels, is sensitive to Kv channel activity, and is in turn critically important for DC maturation and functions.

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“…21,49 During myelination and demyelination, Kv1.4 is particularly expressed on oligodendroglial cells. Kv1.4 expression is not found on immune cells, although the expression of the related channels Kv1.3 and Kv1.5 may be involved in T-cell activation and dendritic cell function in EAE and MS. 29,30,50,51 During oligodendroglial development in vitro, there is a clear coexpression of Kv1.4 with AN2 in cells, which at a certain stage are also CNPase-positive. During MOG-EAE in vivo, Kv1.4 is only found on very few AN2-positive cells, which are also CNPase-positive.…”

Section: Discussionmentioning

confidence: 99%

“…26 In particular, the Kv1.4 subunit has been associated with proliferation in pathological states such as spinal cord injury, 27,28 whereas Kv1.3 and 1.5 are expressed in T cells and dendritic cells during autoimmune demyelination. 29,30 Here, we investigate the expression of Kv1.4 potassium channels in myelin oligodendrocyte glycoprotein peptide )-induced experimental autoimmune encephalomyelitis, an experimental model mimicking aspects of MS, in particular myelin damage and loss of OLs. 31 Our data reveal a re-expression of this developmentally restricted potassium channel in proliferating premyelinating oligodendroglial cells after autoimmune demyelination and suggest a role for Kv1.4 in oligodendroglial proliferation and remyelination.…”

mentioning

confidence: 99%

Re-Expression of a Developmentally Restricted Potassium Channel in Autoimmune Demyelination

Herrero-Herranz¹,

Pardo²,

Bunt³

et al. 2007

The American Journal of Pathology

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Mechanisms of lesion repair in multiple sclerosis are incompletely understood. To some degree, remyelination can occur, associated with an increase of proliferating oligodendroglial cells. Recently, the expression of potassium channels has been implicated in the control of oligodendrocyte precursor cell proliferation in vitro. We investigated the expression of Kv1.4 potassium channels in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis, a model of multiple sclerosis. Confocal microscopy revealed expression of Kv1.4 in AN2-positive oligodendrocyte precursor cells and premyelinating oligodendrocytes in vitro but neither in mature oligodendrocytes nor in the spinal cords of healthy adult mice. After induction of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis, Kv1.4 immunoreactivity was detected in or around lesions already during disease onset with a peak early and a subsequent decrease in the late phase of the disease. Kv1.4 expression was confined to 2,3-cyclic nucleotide 3-phosphodiesterase-positive oligodendroglial cells, which were actively proliferating and ensheathed naked axons. After a demyelinating episode, the number of Kv1.4 and 2,3-cyclic nucleotide 3-phosphodiesterase double-positive cells was greatly reduced in ciliary neurotrophic factor knockout mice, a model with impaired lesion repair. In summary, the re-expression of an oligodendroglial potassium channel may have a functional implication on oligodendroglial cell cycle progression, thus influencing tissue repair in experimental autoimmune encephalomyelitis and multiple sclerosis.

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Potassium channels K_v1.3 and K_v1.5 are expressed on blood‐derived dendritic cells in the central nervous system

Abstract: These data support a functional role of K(v)1.5 and K(v)1.3 on activated human DCs and further define the mechanisms by which K(+) channel blockade may act to suppress immune-mediated neurological diseases.

Cited by 57 publications

References 44 publications

Dendritic cells are abundant in non-lesional gray matter in multiple sclerosis

Dendritic cells are abundant in non-lesional gray matter in multiple sclerosis

Ion Channels Modulating Mouse Dendritic Cell Functions

Re-Expression of a Developmentally Restricted Potassium Channel in Autoimmune Demyelination

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Potassium channels Kv1.3 and Kv1.5 are expressed on blood‐derived dendritic cells in the central nervous system

Abstract: These data support a functional role of K(v)1.5 and K(v)1.3 on activated human DCs and further define the mechanisms by which K(+) channel blockade may act to suppress immune-mediated neurological diseases.

Cited by 57 publications

References 44 publications

Dendritic cells are abundant in non-lesional gray matter in multiple sclerosis

Dendritic cells are abundant in non-lesional gray matter in multiple sclerosis

Ion Channels Modulating Mouse Dendritic Cell Functions

Re-Expression of a Developmentally Restricted Potassium Channel in Autoimmune Demyelination

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Product

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Potassium channels K_v1.3 and K_v1.5 are expressed on blood‐derived dendritic cells in the central nervous system