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Thromboxane A2 modulates interaction of dendritic cells and T cells and regulates acquired immunity

Nature Immunology volume 4, pages 694–701 (2003)Cite this article

Abstract

Physical interaction of T cells and dendritic cells (DCs) is essential for T cell proliferation and differentiation, but it has been unclear how this interaction is regulated physiologically. Here we show that DCs produce thromboxane A2 (TXA2), whereas naive T cells express the thromboxane receptor (TP). In vitro, a TP agonist enhances random cell movement (chemokinesis) of naive but not memory T cells, impairs DC–T cell adhesion, and inhibits DC-dependent proliferation of T cells. In vivo, immune responses to foreign antigens are enhanced in TP-deficient mice, which also develop marked lymphadenopathy with age. Similar immune responses were seen in wild-type mice treated with a TP antagonist during the sensitization period. Thus, TXA2-TP signaling modulates acquired immunity by negatively regulating DC–T cell interactions.

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Figure 1: Lymphadenopathy in aged TP-deficient mice.
Figure 2: TP expression and TXA2 production.
Figure 3: Inhibition of DC-dependent T cell proliferation by I-BOP.
Figure 4: Inhibition of T cell adhesion by I-BOP.
Figure 5: Enhanced chemokinesis of naive T cells by I-BOP.
Figure 6: Enhanced CHS responses in TP-deficient mice.
Figure 7: Skin responses after repetitive DNFB challenge in TP-deficient mice.

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Acknowledgements

We thank Y. Kataoka for injection of embryonic stem cells; T. Furuyashiki, Y. Arakawa, H. Bito, M. Hirashima, N. Minato, Y. Miyachi, J. Cyster and S. Nishikawa for helpful discussion; K. Deguchi and T. Fujiwara for animal breeding; and T. Arai for secretarial assistance. This work was supported by Grants-in-Aid from the Ministry of Education, Science, Sports and Culture of Japan and from the Organization for Pharmaceutical Safety and Research.

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  1. Kenji Kabashima and Takahiko Murata: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto, 606-8501, Japan

    Kenji Kabashima, Takahiko Murata, Toshiyuki Matsuoka, Daiji Sakata & Shuh Narumiya

  2. Department of Dermatology, Kyoto University Faculty of Medicine, Kyoto, 606-8501, Japan

    Kenji Kabashima

  3. Department of Pharmacology, Gifu Pharmaceutical University, Gifu, 502-8585, Japan

    Hiroyuki Tanaka & Hiroichi Nagai

  4. Institute of Medical Science, University of Tokyo, Tokyo, 108-8639, Japan

    Nobuaki Yoshida

  5. Department of Molecular Immunology and Allergy, Kyoto University Faculty of Medicine, Kyoto, 606-8501, Japan

    Koko Katagiri & Tatsuo Kinashi

  6. Molecular and Cellular Recognition, Osaka University Graduate School of Medicine, Suita, 565-0871, Japan

    Toshiyuki Tanaka & Masayuki Miyasaka

  7. Department of Pharmacology, Asahikawa Medical College, Asahikawa, 078-8510, Japan

    Fumitaka Ushikubi

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Correspondence to Shuh Narumiya.

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This work was supported in part by a grant from Ono Pharmaceutical Co. Ltd., Osaka, Japan.

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Kabashima, K., Murata, T., Tanaka, H. et al. Thromboxane A2 modulates interaction of dendritic cells and T cells and regulates acquired immunity. Nat Immunol 4, 694–701 (2003). https://doi.org/10.1038/ni943

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