Nature Immunology
4, 694 - 701 (2003)
Published online: 1 June 2003; | doi:10.1038/ni943
Thromboxane A2 modulates interaction of dendritic cells and T cells and regulates acquired immunityKenji Kabashima1, 2, 8, Takahiko Murata1, 8, Hiroyuki Tanaka3, Toshiyuki Matsuoka1, Daiji Sakata1, Nobuaki Yoshida4, Koko Katagiri5, Tatsuo Kinashi5, Toshiyuki Tanaka6, Masayuki Miyasaka6, Hiroichi Nagai3, Fumitaka Ushikubi7
& Shuh Narumiya11
Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto 606-8501, Japan. 2
Department of Dermatology, Kyoto University Faculty of Medicine, Kyoto 606-8501, Japan. 3
Department of Pharmacology, Gifu Pharmaceutical University, Gifu 502-8585, Japan. 4
Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan. 5
Department of Molecular Immunology and Allergy, Kyoto University Faculty of Medicine, Kyoto 606-8501, Japan. 6
Molecular and Cellular Recognition, Osaka University Graduate School of Medicine, Suita 565-0871, Japan. 7
Department of Pharmacology, Asahikawa Medical College, Asahikawa 078-8510, Japan. 8
These authors contributed equally to this work.
Correspondence should be addressed to Shuh Narumiya snaru@mfour.med.kyoto-u.ac.jpPhysical 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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