Increased Th2-like Invariant Natural Killer T cells in Peripheral Blood From Patients With Asthma

Shim, Jae Uoong; Koh, Young Il

doi:10.4168/aair.2014.6.5.444

Cited by 23 publications

(14 citation statements)

References 20 publications

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“…We previously showed that the frequency of IL-4-producing iNKT cells was inversely correlated with the degree of lung function in asthmatic patients, suggesting the contribution of Th2-like iNKT cells in uncontrolled asthma. 13 Th17-like iNKT cells play a critical role in a mouse model of ozone-induced neutrophilic asthma 6 and have also been reported in humans. 34 Furthermore, iNKT cells express Foxp3 in healthy individuals.…”

Section: Discussionmentioning

confidence: 99%

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Flagellin Modulates the Function of Invariant NKT Cells From Patients With Asthma via Dendritic Cells

Shim

Rhee

Jeong

et al. 2016

Allergy Asthma Immunol Res

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PurposeInvariant natural killer T (iNKT) cells play a critical role in the pathogenesis of asthma. We previously reported the association between circulating Th2-like iNKT cells and lung function in asthma patients and the suppressive effect of Toll-like receptor 5 ligand flagellin B (FlaB) on asthmatic in a mouse model. Thus, we investigated whether FlaB modulates the function of circulating iNKT cells in asthmatic patients.MethodsPeripheral blood mononuclear cells (PBMCs) were treated with FlaB, and the secreted and intracellular cytokines of iNKT cells were evaluated by using ELISA and flow cytometry, respectively, following stimulation with α-galactosylceramide. Foxp3+ iNKT cells were also measured. To determine the effect of FlaB-treated dendritic cells (DCs) on iNKT cells, we co-cultured CD14+ monocyte-derived DCs and T cells from patients with house dust mite-sensitive asthma and analyzed intracellular cytokines in iNKT cells.ResultsA reduction of IL-4 and IL-17 production by iNKT cells in PBMCs after FlaB treatment was alleviated following blocking of IL-10 signaling. A decrease in the frequencies of IL-4+ and IL-17+ iNKT cells by FlaB-treated DCs was reversed after blocking of IL-10 signaling. Simultaneously, an increase in Foxp3+ iNKT cells induced by FlaB treatment disappeared after blocking of IL-10.ConclusionsFlaB may inhibit Th2- and Th17-like iNKT cells and induce Foxp3+ iNKT cells by DCs via an IL-10-dependent mechanism in asthmatic patients. In patients with a specific asthma phenotype associated with iNKT cells, FlaB may be an effective immunomodulator for iNKT cell-targeted immunotherapy.

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Section: Discussionmentioning

confidence: 99%

“… 12 Indeed, we revealed that circulating iNKT cells were Th2-like and related to lung function in asthma patients. 13 …”

Section: Introductionmentioning

confidence: 99%

Flagellin Modulates the Function of Invariant NKT Cells From Patients With Asthma via Dendritic Cells

Shim

Rhee

Jeong

et al. 2016

Allergy Asthma Immunol Res

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“…Akbari et al showed that lung CD4+ iNKT cells from asthmatics secreted both IL-4 and IL-13 but little IFN-γ on αGalCer stimulation [ 12 ]. However, conclusions about the contribution of peripheral blood iNKT cells from asthmatics to the severity of asthma have been equivocal [ 13 – 16 ]. Nonetheless, iNKT cells play an essential role in viral and pediatric exacerbations of asthma and in severe asthma [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

β-Catenin is required for the differentiation of iNKT2 and iNKT17 cells that augment IL-25-dependent lung inflammation

et al. 2015

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BackgroundInvariant Natural Killer T (iNKT) cells have been implicated in lung inflammation in humans and also shown to be a key cell type in inducing allergic lung inflammation in mouse models. iNKT cells differentiate and acquire functional characteristics during development in the thymus. However, the correlation between development of iNKT cells in the thymus and role in lung inflammation remains unknown. In addition, transcriptional control of differentiation of iNKT cells into iNKT cell effector subsets in the thymus during development is also unclear. In this report we show that β-catenin dependent mechanisms direct differentiation of iNKT2 and iNKT17 subsets but not iNKT1 cells.MethodsTo study the role for β-catenin in lung inflammation we utilize mice with conditional deletion and enforced expression of β-catenin in a well-established mouse model for IL-25-dependen lung inflammation.ResultsSpecifically, we demonstrate that conditional deletion of β-catenin permitted development of mature iNKT1 cells while impeding maturation of iNKT2 and 17 cells. A role for β-catenin expression in promoting iNKT2 and iNKT17 subsets was confirmed when we noted that enforced transgenic expression of β-catenin in iNKT cell precursors enhanced the frequency and number of iNKT2 and iNKT17 cells at the cost of iNKT1 cells. This effect of expression of β-catenin in iNKT cell precursors was cell autonomous. Furthermore, iNKT2 cells acquired greater capability to produce type-2 cytokines when β-catenin expression was enhanced.DiscussionThis report shows that β-catenin deficiency resulted in a profound decrease in iNKT2 and iNKT17 subsets of iNKT cells whereas iNKT1 cells developed normally. By contrast, enforced expression of β-catenin promoted the development of iNKT2 and iNKT17 cells. It was important to note that the majority of iNKT cells in the thymus of C57BL/6 mice were iNKT1 cells and enforced expression of β-catenin altered the pattern to iNKT2 and iNKT17 cells suggesting that β-catenin may be a major factor in the distinct pathways that critically direct differentiation of iNKT effector subsets.ConclusionsThus, we demonstrate that β-catenin expression in iNKT cell precursors promotes differentiation toward iNKT2 and iNKT17 effector subsets and supports enhanced capacity to produce type 2 and 17 cytokines which in turn augment lung inflammation in mice.

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“…Several studies have analyzed the possible implication of iNKT cells in the physiopathology of human asthma. Studies analyzing the frequency of iNKT cells in the [bronchoalveolar-lavage fluid (BALF)] or bronchial tissues of asthmatic patients have reported discordant results ( 67 – 70 ). The study of Akbari et al ( 68 ) found that about 60% of the pulmonary CD4 + CD3 + T cells in adult patients with moderate-to-severe persistent asthma were iNKT cells.…”

Section: Inkt Cellsmentioning

confidence: 99%

Invariant Natural Killer T and Mucosal-Associated Invariant T Cells in Asthmatic Patients

Lezmi

Leite‐de‐Moraes

2018

Front. Immunol.

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Recent studies have highlighted the heterogeneity of asthma. Distinct patient phenotypes (symptoms, age at onset, atopy, and lung function) may result from different pathogenic mechanisms, including airway inflammation, remodeling, and immune and metabolic pathways in a specific microbial environment. These features, which define the asthma endotype, may have significant consequences for the development and progression of the disease. Asthma is generally associated with Th2 cells, which produce a panel of cytokines (IL-4, IL-5, IL-13) that act in synergy to drive lung inflammatory responses, mucus secretion, IgE production, and fibrosis, causing the characteristic symptoms of asthma. In addition to conventional CD4+ T lymphocytes, other T-cell types can produce Th2 or Th17 cytokines rapidly. Promising candidate cells for studies of the mechanisms underlying the pathophysiology of asthma are unconventional T lymphocytes, such as invariant natural killer T (iNKT) and mucosal-associated invariant T (MAIT) cells. This review provides an overview of our current understanding of the impact of iNKT and MAIT cells on asthmatic inflammation, focusing particularly on pediatric asthma.

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Increased Th2-like Invariant Natural Killer T cells in Peripheral Blood From Patients With Asthma

Cited by 23 publications

References 20 publications

Flagellin Modulates the Function of Invariant NKT Cells From Patients With Asthma via Dendritic Cells

Flagellin Modulates the Function of Invariant NKT Cells From Patients With Asthma via Dendritic Cells

β-Catenin is required for the differentiation of iNKT2 and iNKT17 cells that augment IL-25-dependent lung inflammation

Invariant Natural Killer T and Mucosal-Associated Invariant T Cells in Asthmatic Patients

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