Protective role of interleukin-10-producing regulatory dendritic cells against murine autoimmune gastritis.
BACKGROUND
Regulatory dendritic cells (Reg-DCs), which induce regulatory T cells and interleukin (IL)-10 in vitro, are capable of inducing immunogenic tolerance in vivo. In this study, we assessed whether Reg-DCs modulate the course of autoimmune processes in a murine model of autoimmune gastritis (AIG).


METHODS
AIG mice were produced by neonatal thymectomy of 3-day old BALB/c mice followed by administration of polyinosinic:polycytidylic acid (poly I:C). Reg-DCs were produced by culturing bone marrow DCs with IL-10, lipopolysaccharide, and parietal cell (PC) antigen for 2 days. In the course of development of AIG, BALB/c mice were administered either Reg-DCs, mature DCs, or phosphate-buffered saline, intraperitoneally, four times. The levels of gastritis and autoantibody to PC antigen were assessed serially in these mice.


RESULTS
The stages of gastritis and the titers of autoantibody to PC antigen were significantly lower in Reg-DC-treated mice than in mature DC-treated mice (P<0.05). Spleen cells from Reg-DC-treated mice produced increased levels of IL-10 and decreased levels of IL-12p70 and interferon-gamma (P<0.05). Also, frequencies of IL-10-producing CD4(+)CD25(+) T cells in the spleen and Foxp3(+)CD4(+)CD25(+) T cells in the peripheral blood were significantly higher in Reg-DC-treated mice than in mature DC-treated mice (P<0.05).


CONCLUSIONS
Taken together, these results suggest that increased induction of CD4(+)CD25(+) regulatory T cells by Reg-DCs might contribute to downregulation of inflammatory processes and autoantibody production during AIG development in mice.
Torisu
Masamoto
M
Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, 454 Shitsukawa, Toon, 791-0295, Japan.
Murakami
Hidehiro
H
Akbar
Fazle
F
Matsui
Hidetaka
H
Hiasa
Yoichi
Y
Matsuura
Bunzo
B
Onji
Morikazu
M
D000818:Animals; D001327:Autoimmune Diseases / Q000503:physiopathology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D005434:Flow Cytometry; D005756:Gastritis / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D007167:Immunotherapy; D016753:Interleukin-10 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000502:physiology
D016753:Interleukin-10