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

doi:10.1038/ni943

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 journal › Article › peer-review

149 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 language	English
Pages (from-to)	694-701
Number of pages	8
Journal	Nature Immunology
Volume	4
Issue number	7
DOIs	https://doi.org/10.1038/ni943
Publication status	Published - Jul 1 2003
Externally published	Yes

All Science Journal Classification (ASJC) codes

Immunology and Allergy
Immunology

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title = "Thromboxane A2 modulates interaction of dendritic cells and T cells and regulates acquired immunity",

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.",

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

note = "Funding Information: 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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doi = "10.1038/ni943",

language = "English",

volume = "4",

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T1 - Thromboxane A2 modulates interaction of dendritic cells and T cells and regulates acquired immunity

AU - Kabashima, Kenji

AU - Murata, Takahiko

AU - Tanaka, Hiroyuki

AU - Matsuoka, Toshiyuki

AU - Sakata, Daiji

AU - Yoshida, Nobuaki

AU - Katagiri, Koko

AU - Kinashi, Tatsuo

AU - Tanaka, Toshiyuki

AU - Miyasaka, Masayuki

AU - Nagai, Hiroichi

AU - Ushikubi, Fumitaka

AU - Narumiya, Shuh

N1 - Funding Information: 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.

PY - 2003/7/1

Y1 - 2003/7/1

N2 - 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.

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

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