Atopic Dermatitis and V<sub>α</sub>24<sup>+</sup> Natural Killer T Cells

Ilhan, Fulya; Kandı, Başak; Akbulut, Handan; Turgut, Dilara; Çiçek, Demet

doi:10.1111/j.1540-9740.2007.06458.x

Cited by 16 publications

(8 citation statements)

References 12 publications

(25 reference statements)

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“…The findings above suggest a scenario where the chronically increased IL‐18 levels seen in AE patients alone could suffice to induce a chronic stimulation and subsequent decrease in iNKT‐cells. In line with this reasoning, a significant decrease in peripheral blood iNKT‐cells has previously been observed in AE patients 26, 27. To follow up on our in vitro findings, we investigated the percentage of iNKT‐cells in peripheral blood of the AE patient cohort.…”

Section: Resultssupporting

confidence: 63%

IL‐18 skews the invariant NKT‐cell population via autoreactive activation in atopic eczema

et al. 2009

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Atopic eczema (AE) is a chronic relapsing inflammatory skin disease where the commensal yeast Malassezia can act as a microbial trigger factor. Malassezia activates human DC to produce IL-18, an innate cytokine that is elevated in serum of AE patients; however, the precise role of IL-18 in human AE etiology is unknown. Herein, we investigated the effect of IL-18 on the human invariant NKT (iNKT) cell compartment in AE. We found that IL-18 was a potent activator of human iNKT-cells and promoted a proinflammatory CD1d-dependent response, even in the absence of exogenous ligands. Chronic activation via IL-18 on the other hand was inhibitory and skewed the iNKT-cell pool by selectively suppressing CD41 iNKT-cells. This was mimicked in AE patients where the proportion of CD4 1 iNKT-cells was reduced in peripheral blood and coincided with elevated plasma levels of IL-18. Furthermore, a reduced CD4 1 iNKT-cell pool was associated with elevated IgE levels in plasma, and the plasma levels of IL-18 correlated with both total IgE and disease severity in the AE patients. Based on these findings, we propose that IL-18-mediated activation and subsequent dysregulation of the CD1d-restricted iNKTcells plays a role in the pathogenesis of human AE.Key words: Allergy . Autoreactivity . IL-18 . Inflammation . NKT cells Supporting Information available online IntroductionAtopic eczema (AE) is a common chronic relapsing inflammatory skin disease affecting 15-30% of children and 2-10% of adults in industrialized countries [1]. The disease has a complex etiology including genetic predisposition as well as environmental triggers such as the gram-positive bacteria Staphylococcus aureus and the commensal yeast Malassezia sympodialis [1,2]. Approximately 50% of adult AE patients have serum IgE specific for M. sympodialis, while such reactivity is rare in other allergic Ã These authors contributed equally to this work. iNKT-cells are innate-like T cells that operate on the border between the innate and adaptive immune response. They can promote both Th1 or Th2 type cytokine responses and work as both pro-inflammatory and tolerogenic cells in the immune response [12,13]. Human iNKT-cells express an invariant TCR carrying Va24 and Vb11 segments, which recognizes glycolipid antigens presented by the MHC class I-like molecule CD1d. These antigens include both foreign glycolipids such as bacterial antigens or allergen-derived ligands as well as self-ligands [13,14]. Thus, the nature of the TCR used by iNKT-cell renders them reactive to self-antigens [15]. There are CD41 and CD4 À subtypes of iNKT-cells and they have in common that they respond rapidly to antigen stimulation with a high level of IFN-g production [13]. Human iNKT-cell subsets, however, differ in that the CD4 1 subset produce Th2-type cytokines such as IL-4 and IL-13 whereas the CD4 À subset do not [16][17][18]. The role of iNKT-cells in atopic diseases is controversial. The findings reported from human and mouse studies are somewhat contradictory and at the present there is no con...

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Section: Resultssupporting

confidence: 63%

IL‐18 skews the invariant NKT‐cell population via autoreactive activation in atopic eczema

et al. 2009

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“…In agreement with our results, four previous publications demonstrated diminished numbers of iNKT cells in AD patients; conversely, two groups found increased numbers of these cells [25,[40][41][42][43]26]. These contradictory results suggest that further investigations are needed, as it is possible that not only differences in the applied methods but also differences in the patient selection (extrinsic-intrinsic AD, mild-moderate-severe AD) may alter the iNKT cell number.…”

Section: Discussionsupporting

confidence: 87%

Altered Peripheral Invariant Natural Killer T Cells in Atopic Dermatitis

et al. 2011

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“…30 Others have reported, however, that iNKT cell levels in the peripheral blood of patients with AD are lower or not significantly different than HCs. [31][32][33][34][35] Elevated iNKT cells in PBMCs of patients with AD may come from increased levels of the activated, circulating Tcell pool in patients with AD. 36 Similarly, there are increased numbers of peripheral blood regulatory T cells in patients with AD.…”

Section: Discussionmentioning

confidence: 98%

Thymic stromal lymphopoietin–activated invariant natural killer T cells trigger an innate allergic immune response in atopic dermatitis

Park

et al. 2010

Journal of Allergy and Clinical Immunology

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Atopic Dermatitis and V_α24⁺ Natural Killer T Cells

Abstract: The reduction of Valpha24+CD161+ NKT cells subtypes may be involved in the immunopathogenesis of atopic dermatitis.

Cited by 16 publications

References 12 publications

IL‐18 skews the invariant NKT‐cell population via autoreactive activation in atopic eczema

IL‐18 skews the invariant NKT‐cell population via autoreactive activation in atopic eczema

Altered Peripheral Invariant Natural Killer T Cells in Atopic Dermatitis

Thymic stromal lymphopoietin–activated invariant natural killer T cells trigger an innate allergic immune response in atopic dermatitis

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Atopic Dermatitis and Vα24+ Natural Killer T Cells

Abstract: The reduction of Valpha24+CD161+ NKT cells subtypes may be involved in the immunopathogenesis of atopic dermatitis.

Cited by 16 publications

References 12 publications

IL‐18 skews the invariant NKT‐cell population via autoreactive activation in atopic eczema

IL‐18 skews the invariant NKT‐cell population via autoreactive activation in atopic eczema

Altered Peripheral Invariant Natural Killer T Cells in Atopic Dermatitis

Thymic stromal lymphopoietin–activated invariant natural killer T cells trigger an innate allergic immune response in atopic dermatitis

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Atopic Dermatitis and V_α24⁺ Natural Killer T Cells