The inhibition of cutaneous T cell apoptosis may prevent resolution of inflammation in atopic eczema

Orteu, Catherine H.; Rustin, M.H.A.; O'Toole, EA; Sabin, Caroline; Salmon, Mike; Poulter, L. W.; Akbar, Arne N.

doi:10.1046/j.1365-2249.2000.01333.x

Cited by 24 publications

(27 citation statements)

References 18 publications

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“…This is of interest because IFN-producing CD8 ϩ T cells may play a crucial role in the development and maintenance of chronic atopic dermatitis (31). A recent study suggests that IL-15 may act as an anti-apoptotic cytokine in the maintenance of chronic AD (32). The role of IL-15 in sustaining chronic skin inflammation have been supported by the studies of IL-15 expression in keratinocytes of psoriasis lesions (23) and dermal fibroblast (33).…”

Section: Discussionmentioning

confidence: 98%

Decreased IL-15 May Contribute to Elevated IgE and Acute Inflammation in Atopic Dermatitis

Ong

Hamid

Travers

et al. 2002

The Journal of Immunology

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PBMC and acute skin lesions of patients with atopic dermatitis (AD) are characterized by increased IL-4 and IL-13, but decreased IFN-γ production. This bias toward an increased Th2 cytokine profile may contribute to the elevated IgE levels and acute skin inflammation seen in AD. In this study, we examined the levels of IL-15, a Th1-like cytokine, in the PBMC and the skin lesions of AD patients. IL-15 secretion by Staphylococcal enterotoxin B-treated PBMC of AD patients was significantly lower than that of normals and psoriasis patients (p < 0.001). Membrane-bound IL-15 expression as measured by mean fluorescence intensity and percentage of IL-15-positive cells in Staphylococcal enterotoxin B-treated monocytes of AD patients (644 ± 49% and 12.7 ± 0.6%, respectively) were significantly lower than that of normals (869 ± 56% and 15.8 ± 1.2%, respectively) and psoriasis patients (1488 ± 217% and 22.7 ± 0.8%, respectively; p < 0.0007 and p < 0.0001, respectively). The membrane-bound IL-15 expression was also significantly lower in the control monocytes of AD patients compared with that in normals and psoriasis patients. There was no significant difference in the absolute number or percentage of monocytes between the study subjects. However, psoriasis skin lesions were found to have significantly more IL-15 mRNA-expressing cells (22.4 ± 1.7) compared with that in acute AD (7.5 ± 1.7) and chronic AD (13.7 ± 1.7) skin lesions (p < 0.05). IL-15 enhanced IFN-γ production by the PBMC of AD patients (p < 0.01), but not by that of normal individuals or psoriasis patients. In addition, IL-15 was found to suppress IgE synthesis (p < 0.01) by the PBMC of AD patients. These data support the concept that reduced IL-15 expression may contribute to the pathogenesis of AD.

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Section: Discussionmentioning

confidence: 98%

Decreased IL-15 May Contribute to Elevated IgE and Acute Inflammation in Atopic Dermatitis

Ong

Hamid

Travers

et al. 2002

The Journal of Immunology

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“…This dysregulated apoptosis is considered to be an important factor in the pathogenesis of AD. 12,13 Thus, IL-10 is an important factor in the pathogenesis of AD, and the regulation of its production is a potential solution for immunotherapeutic intervention.…”

Section: Introductionmentioning

confidence: 99%

Improvement of dermatitis by iontophoretically delivered antisense oligonucleotides for interleukin-10 in NC/Nga mice

et al. 2004

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IL-10 is overexpressed in skin lesions of atopic dermatitis (AD) patients and believed to be an important factor in the pathogenesis of the disease. Thus the regulation of IL-10 production is a potential solution for immunotherapeutic intervention in AD. We examined the topical delivery of an antisense oligonucleotide for mouse IL-10 (AS6) and the therapeutic effect on the skin lesions of NC/Nga mice, a human AD model. Using an iontophoresis system, about 30% of the applied dose of AS6 penetrated the skin and was distributed in the epidermis and upper dermis. Topically delivered AS6 decreased the levels of mRNA and protein of IL-10 in the lesions of NC/Nga mice, with no effect on IL-4 levels. The dorsal lesions of NC/Nga mice disappeared with repeated topical application of AS6. Topically delivered AS6 showed an inhibitory effect on the production of IL-10 in the skin lesions of NC/Nga mice and had a therapeutic effect on the established dermatitis.

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“…Hence the efflux or death of T cells in situ significantly contributes to the resolution of inflammatory responses. Conversely, decreased clearance with accumulation of T cells and/or additional inflammatory cells may result in chronic inflammation (23,24). Although the mechanisms mediating T cell clearance and resolution are still not fully appreciated, recent results indicate that cytokine deprivation and/or their decreased production by T cells plays an essential role in the clearance of T cells from inflamed tissues and consequently in the resolution of inflammation (25,26).…”

mentioning

confidence: 99%

The Docosatriene Protectin D1 Is Produced by TH2 Skewing and Promotes Human T Cell Apoptosis via Lipid Raft Clustering

Ariel

Wang

et al. 2005

Journal of Biological Chemistry

217

193

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Docosahexaenoic acid, a major -3 fatty acid in human brain, synapses, retina, and other neural tissues, displays beneficial actions in neuronal development, cancer, and inflammatory diseases by mechanisms that remain to be elucidated. In this study we found, using lipid mediator informatics employing liquid chromatography-tandem mass spectrometry, that (10,17S)-docosatriene/neuroprotectin D1, now termed protectin D1 (PD1), is generated from docosahexaenoic acid by T helper type 2-skewed peripheral blood mononuclear cells in a lipoxygenase-dependent manner. PD1 blocked T cell migration in vivo, inhibited tumor necrosis factor ␣ and interferon-␥ secretion, and promoted apoptosis mediated by raft clustering. These results demonstrated novel anti-inflammatory roles for PD1 in regulating events associated with inflammation and resolution.

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The inhibition of cutaneous T cell apoptosis may prevent resolution of inflammation in atopic eczema

Cited by 24 publications

References 18 publications

Decreased IL-15 May Contribute to Elevated IgE and Acute Inflammation in Atopic Dermatitis

Decreased IL-15 May Contribute to Elevated IgE and Acute Inflammation in Atopic Dermatitis

Improvement of dermatitis by iontophoretically delivered antisense oligonucleotides for interleukin-10 in NC/Nga mice

The Docosatriene Protectin D1 Is Produced by TH2 Skewing and Promotes Human T Cell Apoptosis via Lipid Raft Clustering

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