A novel subset of mouse NKT cells bearing the IL-17 receptor B responds to IL-25 and contributes to airway hyperreactivity

Terashima, Asuka; Watarai, Hiroshi; Inoue, Sayo; Sekine, Etsuko; Nakagawa, Ryusuke; Hase, Koji; Iwamura, Chiaki; Nakajima, Hiroshi; Nakayama, Toshinori; Taniguchi, Masaru

doi:10.1084/jem.20080698

Cited by 225 publications

(215 citation statements)

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“…The precise way in which IL-25 modulates Jagged1 expression on lymph node DCs is not clear. IL-25 has been shown to act through its cognate receptor to drive allergic inflammatory processes by activating a subset of NKT cells and by inducing the differentiation of Th2 cells from naive CD4 T cells (23,41). In our depletion model, we were unable to detect IL-25 within the lymph nodes of RSV-infected mice suggesting that these mechanisms did not operate.…”

Section: Discussionmentioning

confidence: 63%

NK Cell Deficiency Predisposes to Viral-Induced Th2-Type Allergic Inflammation via Epithelial-Derived IL-25

Kaiko

Phipps²,

Angkasekwinai

et al. 2010

The Journal of Immunology

131

115

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Section: Discussionmentioning

confidence: 63%

NK Cell Deficiency Predisposes to Viral-Induced Th2-Type Allergic Inflammation via Epithelial-Derived IL-25

Kaiko

Phipps²,

Angkasekwinai

et al. 2010

The Journal of Immunology

131

115

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“…Combined with the results that iNKT cells from ThPok-deficient and DKO mice showed significantly increased IL-17A production after stimulation, the data likely reflect the fact that ThPok biases iNKT development towards a population of iNKT-IL-17-producing cells in the thymus. 16,27 As these cells produce less IFN-c and IL-4, 17 the influence of ThPok on liver damage may be indirect, as the damage may be a result of altered iNKT cell development in the thymus. We also used the recombinant adenovirus system to overexpress ThPok in ThPok-deficient mice 3 days prior to injection of aGalCer or vehicle.…”

Section: Discussionmentioning

confidence: 99%

“…[12][13][14] More recently, several investigators have proposed three iNKT sublineages based on thymic development and distinct functions. [14][15][16][17][18] These sublineages include NKT1 cells, which have high expression of the T-box transcription factor T-bet (Th1-like iNKT cells) and secrete large amounts of IFN-c upon stimulation; NKT2 cells highly express GATA-binding protein 3 (GATA-3) (Th2-like iNKT cells) and produce IL-4 upon stimulation, whereas NKT-17 cells (Th17-like iNKT cells) express high levels of retinoic acid receptor-related orphan receptor-ct (RORct) and produce IL-17 under activated conditions. 17 The above description raises the possibility that the function of specific iNKT cell sublineages may be determined by transcriptional programs.…”

Section: Introductionmentioning

confidence: 99%

Runt-related transcription factor 3 is involved in the altered phenotype and function in ThPok-deficient invariant natural killer T cells

et al. 2014

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The interplay between the CD4-lineage transcription factor ThPok and the CD8-lineage transcription factor, runt-related transcription factor 3 (Runx3), in T-cell development has been extensively documented. However, little is known about the roles of these transcription factors in invariant natural killer T (iNKT) cell development. CD1d-restricted iNKT cells are committed to the CD4 1 CD8 2 and CD4 2 CD8 2 sublineages, which respond to antigen stimulation with rapid and potent release of T helper (Th) 1 and Th2 cytokines. However, previous reports have demonstrated a new population of CD8 1 NKT cells in ThPok-deficient mice. In the current study, we sought to determine whether Runx3 was involved in the re-expression of CD8 and function of iNKT cells in the absence of ThPok. We used mice lacking Runx3, ThPok or both and verified that Runx3 was partially responsible for the appearance of CD8 1 iNKT cells in ThPok knockout mice. Additionally, Runx3 participated in the immune response mediated by iNKT cells in a model of a-galactosylceramide-induced acute hepatitis. These results indicate that Runx3 is crucial for the phenotypic and functional changes observed in ThPok-deficient iNKT cells. and the canonical T-cell receptor a (TCRa) chain (Va14-Ja18 in mice and V24-J18 in humans) coupled to specific Vb chains (Vb8, Vb7 and Vb2 in mice and Vb11 in humans). These receptors are responsible for the interaction of NKT cells with CD1d molecules expressed on CD4 1 CD8 1 double-positive (DP) thymocytes. 1 NKT cells are classified into type I (defined as invariant (iNKT) or classical NKT cells) and type II based on the antigens recognized by each and their TCR repertoires. 2 Our study focused on type I NKT cells (hereafter referred to as iNKT cells). iNKT cells recognize the glycosphingolipid antigen a-galactosylceramide (a-GalCer) and a-GalCer loading with the tetrameric form of CD1d is often used to define the iNKT cell subset because of the high affinity of CD1d for the iNKT cell TCR. 3 Although iNKT cells originate from CD4 1 CD8 1 (DP) thymocytes 4 and are selected by MHC class

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“…Interestingly, contrasting with IL-33, IL-25 requires iNKT cells to induce Th2-type airway inflammation [31,32]. Such dissimilar roles of IL-25 and IL-33 could be explained by the fact that IL-25 is not capable of enhancing IFN-g production by iNKT cells [31,32], a function that is requisite for counteracting airway inflammation in response to IL-33.…”

Section: The Anti-inflammatory Action Of Inkt Cells Is Driven By Theimentioning

confidence: 99%

A natural protective function of invariant NKT cells in a mouse model of innate‐cell‐driven lung inflammation

et al. 2011

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Activation of invariant natural killer T (iNKT) cells by treatment with their a-galactosylceramide ligand provides therapeutic benefits in several immune inflammatory settings. Given the artificial nature of this stimulation, the natural regulatory functions of iNKT remain uncertain. Addressing this issue in a mouse model of innate-cell-driven lung inflammation induced by the cytokine/alarmin IL-33 that targets iNKT cells, we found that eosinophil and neutrophil recruitment was markedly increased in treated iNKT cell-deficient (Ja18 KO) mice, as was the local production of eotaxin and keratinocyte chemoattractant chemokines. By contrast, lung inflammation decreased after adoptive transfer of iNKT cells, which restored the WT inflammatory response in Ja18 KO mice. Finally, we established that this natural anti-inflammatory function of iNKT cells depends on their IFN-c production and on endogenous IL-12. Our study provides the first evidence of a protective role of iNKT cells during lung inflammation that does not require pharmacological TCR engagement.Keywords: IL-33 . Inflammation . iNKT cells . Innate cells Supporting Information available online IntroductionInvariant natural killer T (iNKT) cells constitute a population of T cells, which share some characteristics with NK cells. In this regard, they occupy a strategic position between adaptive and innate immunity. iNKT cells are characterized by the expression of an invariant Va14Ja18 antigen receptor, chiefly paired with Vb8.2 in mice and of the invariant Va24Ja18/Vb11 pair in humans (for reviews see [1,2] Frontline key regulatory functions, based on the therapeutic benefits provided by their specific exogenous ligand a-galactosyl ceramide (a-GC) in several models of autoimmunity and allergic asthma (for reviews see [5][6]) [7][8][9][10][11]. However, whether these cells actually play a regulatory role in these pathologies in the absence of pharmacological TCR engagement is still doubtful (for reviews see [6]). The answer to this fundamental question in iNKT cell biology has remained elusive since almost all pathological experimental models of autoimmunity and asthma require an immunization phase that presumably recruits and activates iNKT cells in a non-physiological rather than a disease-specific manner. Hence, there is still no definite evidence that iNKT cells specifically exert natural regulatory functions in the experimental allergic OVA-or ragweed-induced asthma model, in which iNKT cells can promote disease protection [10,11] or induction and/or exacerbation [12][13][14], depending on their mode of activation.Here, we used a novel approach to address this issue in a model of innate-cell-driven lung inflammation induced by , a cytokine that has recently been described as a member of the IL-1 family [16] and credited with alarmin functions [17][18][19]. This strategy is of pathophysiological relevance, considering the well-established role played by iNKT cells during allergic asthma together with the fact that they are effectively targeted and functiona...

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A novel subset of mouse NKT cells bearing the IL-17 receptor B responds to IL-25 and contributes to airway hyperreactivity

Abstract: Airway hypersensitive reaction (AHR) is an animal model for asthma, which is caused or

Cited by 225 publications

References 32 publications

NK Cell Deficiency Predisposes to Viral-Induced Th2-Type Allergic Inflammation via Epithelial-Derived IL-25

NK Cell Deficiency Predisposes to Viral-Induced Th2-Type Allergic Inflammation via Epithelial-Derived IL-25

Runt-related transcription factor 3 is involved in the altered phenotype and function in ThPok-deficient invariant natural killer T cells

A natural protective function of invariant NKT cells in a mouse model of innate‐cell‐driven lung inflammation

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