RT Journal Article
SR Electronic
T1 The UDP-Glucose Receptor P2RY14 Triggers Innate Mucosal Immunity in the Female Reproductive Tract by Inducing IL-8
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 7074
OP 7084
DO 10.4049/jimmunol.0900001
VO 182
IS 11
A1 Arase, Toru
A1 Uchida, Hiroshi
A1 Kajitani, Takashi
A1 Ono, Masanori
A1 Tamaki, Kayoko
A1 Oda, Hideyuki
A1 Nishikawa, Sayaka
A1 Kagami, Maki
A1 Nagashima, Takashi
A1 Masuda, Hirotaka
A1 Asada, Hironori
A1 Yoshimura, Yasunori
A1 Maruyama, Tetsuo
YR 2009
UL http://www.jimmunol.org/content/182/11/7074.abstract
AB Innate mucosal immune responses, including recognition of pathogen-associated molecular patterns through Toll-like receptors, play an important role in preventing infection in the female reproductive tract (FRT). Damaged cells release nucleotides, including ATP and uridine 5′-diphosphoglucose (UDP-glucose), during inflammation and mechanical stress. We show in this report that P2RY14, a membrane receptor for UDP-glucose, is exclusively expressed in the epithelium, but not the stroma, of the FRT in humans and mice. P2RY14 and several proinflammatory cytokines, such as IL-8, are up-regulated in the endometria of patients with pelvic inflammatory disease. UDP-glucose stimulated IL-8 production via P2RY14 in human endometrial epithelial cells but not stromal cells. Furthermore, UDP-glucose enhanced neutrophil chemotaxis in the presence of a human endometrial epithelial cell line in an IL-8-dependent manner. Administration of UDP-glucose into the mouse uterus induced expression of macrophage inflammatory protein-2 and keratinocyte-derived cytokine, two murine chemokines that are functional homologues of IL-8, and augmented endometrial neutrophil recruitment. Reduced expression of P2RY14 by small interfering RNA gene silencing attenuated LPS- or UDP-glucose-induced leukocytosis in the mouse uterus. These results suggest that UDP-glucose and its receptor P2RY14 are key front line players able to trigger innate mucosal immune responses in the FRT bypassing the recognition of pathogen-associated molecular patterns. Our findings would significantly impact the strategic design of therapies to modulate mucosal immunity by targeting P2RY14.