Antigen-induced, tolerogenic CD11c+,CD11b+ dendritic cells are abundant in Peyer's patches during the induction of oral tolerance to type II collagen and suppress experimental collagen-induced arthritis.
OBJECTIVE
Although oral tolerance is a well-known phenomenon, the role of dendritic cells (DCs) is not well characterized. This study was conducted to better understand the differential role played by each Peyer's patch DC subset in the induction of oral tolerance to type II collagen (CII) in murine collagen-induced arthritis (CIA).


METHODS
CII was fed 6 times to DBA/1 mice beginning 2 weeks before immunization, and the effect on arthritis was assessed. We compared the proportion of CD11c+,CD11b+ DCs and CD11c+,CD8alpha+ DCs in the Peyer's patches of CII-fed tolerized and phosphate buffered saline-fed nontolerized mice after the induction of CIA. The immunosuppressive properties of each DC subset were determined using fluorescence-activated cell sorter analysis for intracellular interleukin-10 (IL-10) and IL-12 and mixed lymphocyte culture. The ability of each DC subset to induce CD4+,CD25+ T regulatory cells was also examined. Mice were injected with CII-pulsed CD11c+,CD11b+ DCs isolated from Peyer's patches of tolerized mice, and the effect on CIA was examined.


RESULTS
The severity of arthritis was significantly lower in tolerized mice. The proportion of CD11c+,CD11b+ DCs was increased in the Peyer's patches of tolerized mice and those DCs exhibited immunosuppressive characteristics, such as increased IL-10 production, inhibition of T cell proliferative responses to CII, and CD4+,CD25+ regulatory T cell induction. Furthermore, the CD11c+,CD11b+ DCs suppressed the severity of arthritis upon adoptive transfer.


CONCLUSIONS
Our observations demonstrate that CD11c+,CD11b+ DCs, which are abundant in Peyer's patches during the induction of oral tolerance to CII, are crucial for the suppression of CIA and could be exploited for immunotherapy of autoimmune diseases.
Min
So-Youn
SY
Rheumatism Research Center, The Catholic University of Korea, Seocho-Ku, Seoul, Korea.
Park
Kyung-Su
KS
Cho
Mi-La
ML
Kang
Jung-Won
JW
Cho
Young-Gyu
YG
Hwang
Sue-Yun
SY
Park
Min-Jung
MJ
Yoon
Chong-Hyeon
CH
Min
Jun-Ki
JK
Lee
Sang-Heon
SH
Park
Sung-Hwan
SH
Kim
Ho-Youn
HY
D019264:Adoptive Transfer; D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000517:prevention & control; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control; D039481:CD11b Antigen / Q000032:analysis*; D039521:CD11c Antigen / Q000032:analysis*; D016827:CD8 Antigens / Q000032:analysis; D024043:Collagen Type II / Q000008:administration & dosage / Q000276:immunology*; D003713:Dendritic Cells / Q000502:physiology*; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000032:analysis; D018664:Interleukin-12 / Q000032:analysis; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010581:Peyer's Patches / Q000166:cytology / Q000276:immunology*
D039481:CD11b Antigen; D039521:CD11c Antigen; D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D024043:Collagen Type II; D016753:Interleukin-10; D018664:Interleukin-12