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Th9 and other IL-9-producing cells in allergic asthma

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Abstract

Allergic asthma is a worldwide increasing chronic disease of the airways which affects more than 300 million people. It is associated with increased IgE, mast cell activation, airway hyperresponsiveness (AHR), mucus overproduction and remodeling of the airways. Previously, this pathological trait has been associated with T helper type 2 (Th2) cells. Recently, different CD4+ T cell subsets (Th17, Th9) as well as cells of innate immunity, like mast cells and innate lymphoid cells type 2 (ILC2s), which are all capable of producing the rediscovered cytokine IL-9, are known to contribute to this disease. Regarding Th9 cells, it is known that naïve T cells develop into IL-9-producing cells in the presence of interleukin-4 (IL-4) and transforming growth factor beta (TGFβ). Downstream of IL-4, several transcription factors like signal transducer and activator of transcription 6 (STAT6), interferon regulatory factor 4 (IRF4), GATA binding protein 3 (GATA3), basic leucine zipper transcription factor, ATF-like (BATF) and nuclear factor of activated T cells (NFAT) are activated. Additionally, the transcription factor PU.1, which is downstream of TGFβ signaling, also seems to be crucial in the development of Th9 cells. IL-9 is a pleiotropic cytokine that influences various distinct functions of different target cells such as T cells, B cells, mast cells and airway epithelial cells by activating STAT1, STAT3 and STAT5. Because of its pleiotropic functions, IL-9 has been demonstrated to be involved in several diseases, such as cancer, autoimmunity and other pathogen-mediated immune-regulated diseases. In this review, we focus on the role of Th9 and IL-9-producing cells in allergic asthma.

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Acknowledgements

This work has been supported by the Department of Molecular Pneumology and by the Deutsche Forschungsgemeinschaft (DFG grant KO 5404/1-1).

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  1. Department of Molecular Pneumology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Universitätsklinikum Erlangen, 91052, Erlangen, Germany

    Sonja Koch, Nina Sopel & Susetta Finotto

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  1. Sonja Koch
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  2. Nina Sopel
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  3. Susetta Finotto
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Correspondence to Susetta Finotto.

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This article is a contribution to the special issue on Th9 Cells in Immunity and Immunopathological Diseases - Guest Editors: Mark Kaplan and Markus Neurath

Sonja Koch and Nina Sopel contributed equally to this review.

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Koch, S., Sopel, N. & Finotto, S. Th9 and other IL-9-producing cells in allergic asthma. Semin Immunopathol 39, 55–68 (2017). https://doi.org/10.1007/s00281-016-0601-1

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