期刊
ALLERGOLOGY INTERNATIONAL
卷 63, 期 3, 页码 443-455出版社
JAPANESE SOCIETY ALLERGOLOGY
DOI: 10.2332/allergolint.13-OA-0672
关键词
atopic dermatitis; dendritic cells; epithelial cells; Th2 cytokines; Th2 responses
资金
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [21591289, 24591472]
- The Japan Medical Association
- Takeda Science Foundation
- Grants-in-Aid for Scientific Research [24591472, 21591289] Funding Source: KAKEN
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 naive 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 naive 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.
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