Immunoregulatory function of PIR-A/B+ DCs in the inflammatory responses of dextran sodium sulfate-induced colitis.
BACKGROUND
Dendritic cells (DCs) may play an important role in forms of inflammatory bowel disease (IBD), such as Crohn's disease and ulcerative colitis. DCs are generally recognized as initiators of acquired immunity and also serve as regulators of both innate and acquired immunity. We used the animal model of colitis induced by dextran sodium sulfate (DSS), and examined whether DCs prepared from the colon show immunoregulatory roles in the termination of DSS-induced colitis.


METHODS
C57BL/6 mice exposed to DSS for 5 days developed acute colitis. DCs were isolated from the large intestinal lamina propria, and then analyzed for phenotypical, functional, and genetic data.


RESULTS
Only PIR-A/B(low) conventional DCs (cDCs) were detected in the steady state. However, after the treatment of DSS, PIR-A/B(high) cDCs appeared and gradually increased from day 5 to day 7, at which time the DSS-induced colitis was terminated. Then, allogeneic mixed leukocyte reaction (MLR) was performed. The stimulatory activity of PIR-A/B(high) cDCs obtained on day 7 was very low, and the addition of PIR-A/B(high) cDCs suppressed the T cell proliferation in MLR, indicating the immunoregulatory role of PIR-A/B(high) cDCs. The immunoregulatory role of PIR-A/B(high) cDCs was confirmed by the in vivo transfer experiment, showing their therapeutic effect on DSS-induced colitis. The message level of TGFβi was significantly higher in PIR-A/B(high) cDCs, while that of IFN-γ was highly upregulated in PIR-A/B(low) cDCs, being well in accordance with the fact that PIR-A/B(high) cDCs showed a suppressive function against activated T cells.


CONCLUSIONS
PIR-A/B(high) cDCs showed a suppressive function against activated T cells by producing inhibitory cytokines.
Division of Gastroenterology and Hepatology, Third Department of Internal Medicine, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka, 570-8506, Japan, kurishia@takii.kmu.ac.jp.
Akiko
A
Kurishima
Muneo
M
Inaba
Yutaku
Y
Sakaguchi
Toshiro
T
Fukui
Kazushige
K
Uchida
Akiyoshi
A
Nishio
Shosaku
S
Nomura
Kazuichi
K
Okazaki
D019264:Adoptive Transfer; D000818:Animals; D003106:Colon / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D005260:Female; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D007959:Lymphocyte Culture Test, Mixed / Q000379:methods; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011971:Receptors, Immunologic / Q000032:analysis
D011971:Receptors, Immunologic; D016264:Dextran Sulfate