Interleukin-9 Is Required for Allergic Airway Inflammation Mediated by the Cytokine TSLP

Yao, Weiguo; Zhang, Yanlu; Jabeen, Rukhsana; Nguyen, Evelyn T.; Wilkes, David S.; Tepper, Robert S.; Kaplan, Mark H.; Zhou, Baohua

doi:10.1016/j.immuni.2013.01.007

Cited by 165 publications

(161 citation statements)

References 54 publications

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“…Th9 effector cells are distinct from Th2 cells and can be differentiated in vitro via TCR stimulation in the presence of TGF-b and IL-4, or directly in the presence of TSLP [2,4]. Given the pleiotropic functions of IL-9, Th9 cells might be involved in several types of inflammatory disease.…”

Section: Discussionmentioning

confidence: 99%

“…3DI). Since Th9 polarization has been demonstrated to be dependent on IL-4, TGF-b and TSLP [2,4], we next evaluated their expression in synovial tissues from patients and controls. A significant upregulation of IL-4 ( Fig.…”

Section: Il-9 Il-4 Tgf-b Tslp and Th9 Expression In Ra Synovial Samentioning

confidence: 99%

“…In addition to Th1, Th17 and Th2 cells, another subset of effector T cells, identified by the production of IL-9 and named Th9 cells, with a potential role in T-cell-dependent B-cell differentiation, expansion and antibody production, has also been described [2,3]. The development of Th9 cells requires a balance of signals from cytokines such as IL-4 and TGF-b [2], and from epithelial cytokines such as thymic stromal lymphopoietin (TSLP) [4].…”

Section: Introductionmentioning

confidence: 99%

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Potential involvement of IL-9 and Th9 cells in the pathogenesis of rheumatoid arthritis

Ciccia¹,

Guggino

Rizzo

et al. 2015

Rheumatology

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Objective. IL-9 has been shown to be upregulated before the clinical onset of articular disease in RA. The exact role of IL-9 and Th9 cells in RA, however, has not yet been adequately studied. The aim of this study was to evaluate the expression of IL-9 and IL-9-expressing cells in RA patients.Methods. IL-9, IL-9R, PU.1, IL-9, thymic stromal lymphopoietin (TSLP), IL-4 and TGF-b expression was assessed by real-time-PCR in the synovial tissues of RA and OA patients. IL-9, IL-9R, IL-4, TSLP and TGF-b were also investigated by immunohistochemistry. Peripheral CD4 + T cell subsets were studied by flow cytometry analysis before and after incubation with citrullinated peptides.Results. IL-9 was overexpressed in RA synovial tissues and correlated with the degree of histological organization of B and T cells in ectopic lymphoid structures. The majority of IL-9-producing cells were identified as CD3 + cells. Increased mRNA and protein expression of IL-9R, IL-4, TSLP and TGF-b was also observed in RA synovial tissue. Blood peripheral Th9 cells were expanded by citrullinated peptides. Conclusion.These results indicate that Th9 cells and IL-9 were frequently detected in peripheral blood mononuclear cells and synovia of RA patients. A possible pathogenic role for Th9 in RA is discussed.

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Section: Discussionmentioning

confidence: 99%

Section: Il-9 Il-4 Tgf-b Tslp and Th9 Expression In Ra Synovial Samentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Potential involvement of IL-9 and Th9 cells in the pathogenesis of rheumatoid arthritis

Ciccia¹,

Guggino

Rizzo

et al. 2015

Rheumatology

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“…Because the contribution of IL-9 for the development of allergic airways inflammation is well established (33,34,53), we investigated the impact of IL-9 produced by iNKT cells in that condition. Our results show that the presence of IL-9-secreting iNKT cells in the airways, even at low numbers, increases local infiltration by eosinophils and mast cells.…”

Section: Discussionmentioning

confidence: 99%

IL-9 Expression by Invariant NKT Cells Is Not Imprinted during Thymic Development

Monteiro

Agua-Doce

Almeida

et al. 2015

The Journal of Immunology

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Invariant NKT (iNKT) cell thymic development can lead to distinct committed effector lineages, namely NKT1, NKT2, and NKT17. However, following identification of IL-9–producing iNKT cells involved in mucosal inflammation, their development remains unaddressed. In this study, we report that although thymic iNKT cells from naive mice do not express IL-9, iNKT cell activation in the presence of TGF-β and IL-4 induces IL-9 secretion in murine and human iNKT cells. Acquisition of IL-9 production was observed in different iNKT subsets defined by CD4, NK1.1, and neuropilin-1, indicating that distinct functional subpopulations are receptive to IL-9 polarization. Transcription factor expression kinetics suggest that regulatory mechanisms of IL-9 expression are shared by iNKT and CD4 T cells, with Irf4 and Batf deficiency deeply affecting IL-9 production. Importantly, adoptive transfer of an enriched IL-9+ iNKT cell population leads to exacerbated allergic inflammation in the airways upon intranasal immunization with house dust mite, confirming the ability of IL-9–producing iNKT cells to mediate proinflammatory effects in vivo, as previously reported. Taken together, our data show that peripheral iNKT cells retain the capacity of shaping their function in response to environmental cues, namely TGF-β and IL-4, adopting an IL-9–producing NKT cell phenotype able to mediate proinflammatory effects in vivo, namely granulocyte and mast cell recruitment to the lungs.

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“…This suggested that this subset of lymphocytes is a different T-lymphocyte subpopulation characterized by the expression and secretion high amounts IL-9 and IL-10 and hence they were named Th9 lymphocytes. To date, a wide variety of stimuli has been described which contribute to Th9 cell differentiation, as IL-2 [13], IL-25 [50], the peptide related to the calcitonin gene [51], and thymic stromal lymphopoietin [52], among others. This redundancy suggests cell function diversity and heterogeneity.…”

Section: Nkt Cellsmentioning

confidence: 99%

IL-9: Function, Sources, and Detection

Rojas-Zuleta

Sánchez

2017

Methods in Molecular Biology

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IL-9 is a pleiotropic cytokine produced in different amounts by a wide variety of cells including mast cells, NKT cells, Th2, Th17, Treg, ILC2, and Th9 cells. Th9 cells are considered to be the main CD4+ T cells that produce IL-9. IL-9 exerts its effects on multiple types of cells and different tissues. To date, its main role has been found in the immune responses against parasites and pathogenesis of allergic diseases such as asthma and bronchial hyperreactivity. Additionally, it induces the proliferation of hematologic neoplasias, including Hodgkin's lymphoma in humans. However, IL-9 also has antitumor properties in solid tumors such as melanoma. The objective of this review is to describe IL-9, its function, sources, and methods of detection.

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Interleukin-9 Is Required for Allergic Airway Inflammation Mediated by the Cytokine TSLP

Cited by 165 publications

References 54 publications

Potential involvement of IL-9 and Th9 cells in the pathogenesis of rheumatoid arthritis

Potential involvement of IL-9 and Th9 cells in the pathogenesis of rheumatoid arthritis

IL-9 Expression by Invariant NKT Cells Is Not Imprinted during Thymic Development

IL-9: Function, Sources, and Detection

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