Thromboxane A2 modulates interaction of dendritic cells and T cells and regulates acquired immunity.
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.
Kabashima
Kenji
K
Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto 606-8501, Japan.
Murata
Takahiko
T
Tanaka
Hiroyuki
H
Matsuoka
Toshiyuki
T
Sakata
Daiji
D
Yoshida
Nobuaki
N
Katagiri
Koko
K
Kinashi
Tatsuo
T
Tanaka
Toshiyuki
T
Miyasaka
Masayuki
M
Nagai
Hiroichi
H
Ushikubi
Fumitaka
F
Narumiya
Shuh
S
D000818:Animals; D002450:Cell Communication; D002465:Cell Movement; D003713:Dendritic Cells / Q000502:physiology*; D003877:Dermatitis, Contact / Q000209:etiology; D005260:Female; D018960:Hyaluronan Receptors / Q000032:analysis; D007109:Immunity / Q000502:physiology*; D008206:Lymphatic Diseases / Q000209:etiology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017482:Receptors, Thromboxane / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology*; D013928:Thromboxane A2 / Q000502:physiology*
D018960:Hyaluronan Receptors; D017482:Receptors, Thromboxane; D013928:Thromboxane A2