Identification of an IL-17–producing NK1.1neg iNKT cell population involved in airway neutrophilia

Michel, Marie-Laure; Keller, Alexandre C.; Paget, Christophe; Fujio, Masakazu; Trottein, François; Savage, Paul B.; Wong, Chi‐Huey; Schneider, Elke; Dy, Michel; Leite‐de‐Moraes, Maria

doi:10.1084/jem.20061551

Cited by 551 publications

(490 citation statements)

References 31 publications

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“…Since thymic iNKT cells lacking in the expression of NK1.1 and other NK markers can give rise to iNKT cells that express NK1.1 and other NK markers, NK1.1 − iNKT cells are generally perceived as being 'immature' and NK1.1 + iNKT cells as 'mature'. However, a recent report demonstrated the existence of a functionally competent subpopulation of NK1.1 − NKT cells in the lung, which preferentially produces IL-17 [22].…”

Section: The Heterogenous Phenotype Of Inkt Cellsmentioning

confidence: 99%

“…Later studies revealed that while this robust IL-4 production was a signature of iNKT cells, it certainly was not the only cytokine iNKT cells can produce. To date, iNKT cells have been shown to produce IFN-γ and IL-4, as well as IL-2, IL-5, IL-6, IL-10, IL-13, IL-17, IL-21, TNF-α, TGF-β and GM-CSF ( Figure 1A) [21][22][23][24][25][26]. iNKT cells are also known to produce a vast array of chemokines [27].…”

Section: Cytokine and Chemokine Productionmentioning

confidence: 99%

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CD1d-restricted iNKT cells, the ‘Swiss-Army knife’ of the immune system

Matsuda

Mallevaey

Scott‐Browne

et al. 2008

Current Opinion in Immunology

353

399

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SummaryNatural Killer T cells are a distinct lymphocyte lineage that regulates a broad range of immune responses. NKT cells recognize glycolipids presented by the non-classical MHC molecule CD1d. Structural insight into the TCR/glycolipid/CD1d tri-complex has revealed an unusual and unexpected mode of recognition. Recent studies have also identified some of the signaling events during NKT cell development that give NKT cells their innate phenotype. Pathogen-derived glycolipid antigens continue to be found, and new mechanisms of NKT cell activation have been described. Finally, NKT cells have been shown to be remarkably versatile in function during various immune responses. Whether these extensive functional capacities can be attributed to a single population sensitive to environmental cues or if functionally distinct NKT cell subpopulations exist remains unresolved.

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Section: The Heterogenous Phenotype Of Inkt Cellsmentioning

confidence: 99%

Section: Cytokine and Chemokine Productionmentioning

confidence: 99%

CD1d-restricted iNKT cells, the ‘Swiss-Army knife’ of the immune system

Matsuda

Mallevaey

Scott‐Browne

et al. 2008

Current Opinion in Immunology

353

399

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“…In the mouse, CD4 À iNKT cells are more potent to promote tumor rejection [18]. Recently, a new population of CD4 À NK1.1 À iNKT cells producing high levels of the pro-inflammatory cytokine IL-17 together with low IL-4 and IFN-g levels in response to several iNKT cell ligands, has been identified and named iNKT17 cells [19]. Consistent with their ability to produce IL-17 rapidly and independently of IL-6, iNKT17 cells, unlike naive T cells, were found to express constitutively IL-23R and Retinoic acid receptor -related orphan receptor gt (RORgt) [20][21][22].…”

Section: Introductionmentioning

confidence: 99%

NOD mice contain an elevated frequency of iNKT17 cells that exacerbate diabetes

et al. 2011

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Invariant natural killer T (iNKT) cells are a distinct lineage of innate-like T lymphocytes and converging studies in mouse models have demonstrated the protective role of iNKT cells in the development of type 1 diabetes. Recently, a new subset of iNKT cells, producing high levels of the pro-inflammatory cytokine IL-17, has been identified (iNKT17 cells). Since this cytokine has been implicated in several autoimmune diseases, we have analyzed iNKT17 cell frequency, absolute number and phenotypes in the pancreas and lymphoid organs in non-obese diabetic (NOD) mice. The role of iNKT17 cells in the development of diabetes was investigated using transfer experiments. NOD mice exhibit a higher frequency and absolute number of iNKT17 cells in the lymphoid organs as compared with C57BL/6 mice. iNKT17 cells infiltrate the pancreas of NOD mice where they express IL-17 mRNA. Contrary to the protective role of CD4 1 iNKT cells, the CD4 À iNKT cell population, which contains iNKT17 cells, enhances the incidence of diabetes. Treatment with a blocking anti-IL-17 antibody prevents the exacerbation of the disease. This study reveals that different iNKT cell subsets play distinct roles in the regulation of type 1 diabetes and iNKT17 cells, which are abundant in NOD mice, exacerbate diabetes development.

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“…Proliferation, maintenance and full maturation of these cells are controlled by . Recently, it has been shown that IL-17 is produced by diverse T-cell subsets, including CD4 1 T cells, CD8 1 T cells, NKT cells and gd T cells [9][10][11][12]. Physiologically, IL-17 plays a pivotal role in protecting the host against certain infectious microorganisms through the recruitment of neutrophils, by increasing the expression of multiple chemokines [13,14].…”

mentioning

confidence: 99%

Tumor‐infiltrating IL‐17‐producing γδ T cells support the progression of tumor by promoting angiogenesis

et al. 2010

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Based on the evidence that IL-17 is a key cytokine involved in various inflammatory diseases, we explored the critical role of IL-17-producing cd T cells for tumor development in tumor-bearing mouse model. IL-17 À/À mice exhibited a significant reduction of tumor growth, concomitantly with the decrease of vascular density at lesion area, indicating a pro-tumor property of IL-17. Among tumor-infiltrating lymphocytes (TIL), cd T cells were the major cellular source of IL-17. Analysis of TCR repertoires in TIL-cd T cells showed that circulating cd T cells, but not skin resident Vc5 1 cd T cells, produced IL-17. Neutralizing antibodies against IL-23, IL-6, and TGF-b, which were produced within the tumor microenvironment, inhibited the induction of IL-17-producing cd T cells. IL-17 production by tumor-infiltrating cd T cells was blocked by anti-cdTCR or anti-NKG2D antibodies, indicating that these ligands, expressed within the tumor microenvironment, are involved in cd T-cell activation. The IL-17-producing TIL-cd T cells exhibited reduced levels of perforin mRNA expression, but increased levels of COX-2 mRNA expression. Together, our findings support the novel concept that IL-17-producing cd T cells, generated in response to tumor microenvironment, act as tumor-promoting cells by inducing angiogenesis. IntroductionIn order to understand how tumor cells can escape immune surveillance mechanisms and thus develop anti-tumor therapies, it is critically important to investigate the mechanisms by which the immune system interacts with the tumor microenvironment. The tumor microenvironment, which is mainly composed of tumor cells, stromal cells, and tumor-infiltrating immune cells, is entirely different from noncancerous tissues. This unique microenvironment potently inhibits immune responses against tumor cells via various soluble mediators and contact-dependent mechanisms [1,2]. Previously, it was suggested that T-cell Eur. J. Immunol. 2010. 40: 1927-1937 DOI 10.1002 Cellular immune response 1927 responses within the local tumor tissue are completely inhibited. However, this concept was abandoned following the discovery of the regulatory T-cell and Th17 cell subsets, which are activated rather than suppressed in the tumor microenvironment via TGF-b and/or IL-6. Thus, the tumor microenvironment is conducive to IL-17 production. In fact, it has been shown that IL-17 is produced in human and murine tumor tissues [3][4][5]. Tumor cells promote neo-vascularization into tumor tissues through hyperproduction of angiogenic factors, which also support their own abnormal proliferation and survival [6]. It has been reported that tumor cells over-expressing IL-17 significantly promote new vessel growth into the tumor tissues [5]; however, physiological effects of IL-17 on tumor progression remain to be defined. Th17 differentiation from naïve CD4 1 T cells is regulated by TGF-b and IL-6. Proliferation, maintenance and full maturation of these cells are controlled by . Recently, it has been shown that IL-17 is produced by diverse T...

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Identification of an IL-17–producing NK1.1neg iNKT cell population involved in airway neutrophilia

Cited by 551 publications

References 31 publications

CD1d-restricted iNKT cells, the ‘Swiss-Army knife’ of the immune system

CD1d-restricted iNKT cells, the ‘Swiss-Army knife’ of the immune system

NOD mice contain an elevated frequency of iNKT17 cells that exacerbate diabetes

Tumor‐infiltrating IL‐17‐producing γδ T cells support the progression of tumor by promoting angiogenesis

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