IL-33 Promotes the Induction and Maintenance of Th2 Immune Responses by Enhancing the Function of OX40 Ligand

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概要

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• Background: In Th2 immune responses, TSLP is a key player by induction of OX40-ligand (OX40L) on dendritic cells (DCs), which is the trigger to induce Th2 cell-mediated allergic cascade. Thus, TSLP-DC-OX40L axis might be the principal pathway in the inflammatory cascades in atopic dermatitis and asthma. IL-33, which is produced by epithelial cells, has been implicated in the Th2 immune responses and pathogenesis of the allergic disorders. However, the role of IL-33 in the Th2-polarizing TSLP-DC-OX40L axis still remains largely elusive. We focused on the ability of IL-33 to promote OX40L-mediated Th2 responses. Methods: Purified human naï;ve or memory CD4+ T cells were stimulated with recombinant OX40L or TSLP-treated DCs (TSLP-DCs) in the presence of IL-33, and the cytokine production by the primed T cells was examined. We also performed immunohistochemical analyses for the expression of IL-33 in specimens of lymph node and skin from the patients with atopic dermatitis. Results: IL-33 remarkably enhanced TSLP-DCs-driven or OX40L-driven Th2 responses from naïve T cells and the Th2 functional attributes of CRTH2+ CD4+ Th2 memory cells by the increased production of IL-5, IL-9, and IL-13. In addition, IL-33 was expressed in the nuclei of epithelial cells in not only skin lesion but also lymph nodes of the patient with atopic dermatitis, suggesting a specialized role in adaptive T cell-priming phase. Conclusions: IL-33 works as a positive regulator of TSLP-DC-OX40L axis that initiates and maintains the Th2 cell-mediated inflammatory responses, and therefore, it would be a new therapeutic target for the treatment of allergic disorders.

著者

• Ito Tomoki

  First Department Of Internal Medicine Kansai Medical University

• Nomura Shosaku

  First Department Of Internal Medicine Kansai Medical University

• Inaba Muneo

  First Department Of Pathology Kansai Medical University

• Vien Phan

  First Department of Internal Medicine, Kansai Medical University

• Murakami-Satsutani Naoko

  First Department of Internal Medicine, Kansai Medical University

• Nakanishi Takahisa

  First Department of Internal Medicine, Kansai Medical University

• Inagaki Noriko

  First Department of Internal Medicine, Kansai Medical University

• Tanaka Akihiro

  First Department of Internal Medicine, Kansai Medical University

• Kibata Kayoko

  First Department of Internal Medicine, Kansai Medical University

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