CD30 ligand is a target for a novel biological therapy against colitis associated with Th17 responses

Xun Sun, Hisakata Yamada, Kensuke Shibata, Hiromi Muta, Kenzaburo Tani, Eckhard R. Podack, Yoichiro Iwakura, Yasunobu Yoshikai

    Research output: Contribution to journalArticle

    30 Citations (Scopus)

    Abstract

    We have previously found that CD30 ligand (CD30L; CD153)/CD30 signaling executed by the T-T cell interaction plays a critical role in Th17 cell differentiation, at least partly via downregulation of IL-2 production. In this study, we investigated the role of CD30L in the development of colitis experimentally induced by dextran sulfate sodium (DSS), in which IL-17A is involved in the pathogenesis. CD30L-/- mice were resistant to both acute colitis induced by administration of 3 to ∼5% DSS and to chronic colitis induced by administration of 1.5% DSS on days 0-5, 10-15, and 20-25 as assessed by weight loss, survival rate, and histopathology. The levels of IFN-γ, IL-17A, and IL-10 were significantly lower but the IL-2 level higher in the lamina propria T lymphocytes of CD30L-/- mice than those in lamina propria T lymphocytes of wild-type mice after DSS administration. Soluble murine CD30-Ig fusion protein, which was capable of inhibiting Th17 cell differentiation in vitro, ameliorated both types of DSS-induced colitis in wild-type mice. Modulation of CD30L/CD30 signaling by soluble CD30 could be a novel biological therapy for inflammatory diseases associated with Th17 responses.

    Original languageEnglish
    Pages (from-to)7671-7680
    Number of pages10
    JournalJournal of Immunology
    Volume185
    Issue number12
    DOIs
    Publication statusPublished - Dec 15 2010

    Fingerprint

    CD30 Ligand
    Dextran Sulfate
    Biological Therapy
    Colitis
    Th17 Cells
    Interleukin-17
    T-Lymphocytes
    Interleukin-2
    Cell Differentiation
    Mucous Membrane
    Cell Communication
    Interleukin-10
    Weight Loss
    Down-Regulation

    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Immunology

    Cite this

    Sun, X., Yamada, H., Shibata, K., Muta, H., Tani, K., Podack, E. R., ... Yoshikai, Y. (2010). CD30 ligand is a target for a novel biological therapy against colitis associated with Th17 responses. Journal of Immunology, 185(12), 7671-7680. https://doi.org/10.4049/jimmunol.1002229

    CD30 ligand is a target for a novel biological therapy against colitis associated with Th17 responses. / Sun, Xun; Yamada, Hisakata; Shibata, Kensuke; Muta, Hiromi; Tani, Kenzaburo; Podack, Eckhard R.; Iwakura, Yoichiro; Yoshikai, Yasunobu.

    In: Journal of Immunology, Vol. 185, No. 12, 15.12.2010, p. 7671-7680.

    Research output: Contribution to journalArticle

    Sun, X, Yamada, H, Shibata, K, Muta, H, Tani, K, Podack, ER, Iwakura, Y & Yoshikai, Y 2010, 'CD30 ligand is a target for a novel biological therapy against colitis associated with Th17 responses', Journal of Immunology, vol. 185, no. 12, pp. 7671-7680. https://doi.org/10.4049/jimmunol.1002229
    Sun, Xun ; Yamada, Hisakata ; Shibata, Kensuke ; Muta, Hiromi ; Tani, Kenzaburo ; Podack, Eckhard R. ; Iwakura, Yoichiro ; Yoshikai, Yasunobu. / CD30 ligand is a target for a novel biological therapy against colitis associated with Th17 responses. In: Journal of Immunology. 2010 ; Vol. 185, No. 12. pp. 7671-7680.
    @article{8feb9d13d7864a0d971bd26f3237efe3,
    title = "CD30 ligand is a target for a novel biological therapy against colitis associated with Th17 responses",
    abstract = "We have previously found that CD30 ligand (CD30L; CD153)/CD30 signaling executed by the T-T cell interaction plays a critical role in Th17 cell differentiation, at least partly via downregulation of IL-2 production. In this study, we investigated the role of CD30L in the development of colitis experimentally induced by dextran sulfate sodium (DSS), in which IL-17A is involved in the pathogenesis. CD30L-/- mice were resistant to both acute colitis induced by administration of 3 to ∼5{\%} DSS and to chronic colitis induced by administration of 1.5{\%} DSS on days 0-5, 10-15, and 20-25 as assessed by weight loss, survival rate, and histopathology. The levels of IFN-γ, IL-17A, and IL-10 were significantly lower but the IL-2 level higher in the lamina propria T lymphocytes of CD30L-/- mice than those in lamina propria T lymphocytes of wild-type mice after DSS administration. Soluble murine CD30-Ig fusion protein, which was capable of inhibiting Th17 cell differentiation in vitro, ameliorated both types of DSS-induced colitis in wild-type mice. Modulation of CD30L/CD30 signaling by soluble CD30 could be a novel biological therapy for inflammatory diseases associated with Th17 responses.",
    author = "Xun Sun and Hisakata Yamada and Kensuke Shibata and Hiromi Muta and Kenzaburo Tani and Podack, {Eckhard R.} and Yoichiro Iwakura and Yasunobu Yoshikai",
    year = "2010",
    month = "12",
    day = "15",
    doi = "10.4049/jimmunol.1002229",
    language = "English",
    volume = "185",
    pages = "7671--7680",
    journal = "Journal of Immunology",
    issn = "0022-1767",
    publisher = "American Association of Immunologists",
    number = "12",

    }

    TY - JOUR

    T1 - CD30 ligand is a target for a novel biological therapy against colitis associated with Th17 responses

    AU - Sun, Xun

    AU - Yamada, Hisakata

    AU - Shibata, Kensuke

    AU - Muta, Hiromi

    AU - Tani, Kenzaburo

    AU - Podack, Eckhard R.

    AU - Iwakura, Yoichiro

    AU - Yoshikai, Yasunobu

    PY - 2010/12/15

    Y1 - 2010/12/15

    N2 - We have previously found that CD30 ligand (CD30L; CD153)/CD30 signaling executed by the T-T cell interaction plays a critical role in Th17 cell differentiation, at least partly via downregulation of IL-2 production. In this study, we investigated the role of CD30L in the development of colitis experimentally induced by dextran sulfate sodium (DSS), in which IL-17A is involved in the pathogenesis. CD30L-/- mice were resistant to both acute colitis induced by administration of 3 to ∼5% DSS and to chronic colitis induced by administration of 1.5% DSS on days 0-5, 10-15, and 20-25 as assessed by weight loss, survival rate, and histopathology. The levels of IFN-γ, IL-17A, and IL-10 were significantly lower but the IL-2 level higher in the lamina propria T lymphocytes of CD30L-/- mice than those in lamina propria T lymphocytes of wild-type mice after DSS administration. Soluble murine CD30-Ig fusion protein, which was capable of inhibiting Th17 cell differentiation in vitro, ameliorated both types of DSS-induced colitis in wild-type mice. Modulation of CD30L/CD30 signaling by soluble CD30 could be a novel biological therapy for inflammatory diseases associated with Th17 responses.

    AB - We have previously found that CD30 ligand (CD30L; CD153)/CD30 signaling executed by the T-T cell interaction plays a critical role in Th17 cell differentiation, at least partly via downregulation of IL-2 production. In this study, we investigated the role of CD30L in the development of colitis experimentally induced by dextran sulfate sodium (DSS), in which IL-17A is involved in the pathogenesis. CD30L-/- mice were resistant to both acute colitis induced by administration of 3 to ∼5% DSS and to chronic colitis induced by administration of 1.5% DSS on days 0-5, 10-15, and 20-25 as assessed by weight loss, survival rate, and histopathology. The levels of IFN-γ, IL-17A, and IL-10 were significantly lower but the IL-2 level higher in the lamina propria T lymphocytes of CD30L-/- mice than those in lamina propria T lymphocytes of wild-type mice after DSS administration. Soluble murine CD30-Ig fusion protein, which was capable of inhibiting Th17 cell differentiation in vitro, ameliorated both types of DSS-induced colitis in wild-type mice. Modulation of CD30L/CD30 signaling by soluble CD30 could be a novel biological therapy for inflammatory diseases associated with Th17 responses.

    UR - http://www.scopus.com/inward/record.url?scp=78650652886&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=78650652886&partnerID=8YFLogxK

    U2 - 10.4049/jimmunol.1002229

    DO - 10.4049/jimmunol.1002229

    M3 - Article

    VL - 185

    SP - 7671

    EP - 7680

    JO - Journal of Immunology

    JF - Journal of Immunology

    SN - 0022-1767

    IS - 12

    ER -