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

Kenji Kabashima, Takahiko Murata, Hiroyuki Tanaka, Toshiyuki Matsuoka, Daiji Sakata, Nobuaki Yoshida, Koko Katagiri, Tatsuo Kinashi, Toshiyuki Tanaka, Masayuki Miyasaka, Hiroichi Nagai, Fumitaka Ushikubi, Shuh Narumiya

Research output: Contribution to journalArticlepeer-review

136 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)694-701
Number of pages8
JournalNature Immunology
Volume4
Issue number7
DOIs
Publication statusPublished - Jul 1 2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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