Selective expansion of Foxp3-positive regulatory T cells and immunosuppression by suppressors of cytokine signaling 3-deficient dendritic cells

被引:91
作者
Matsumura, Yumiko
Kobayashi, Takashi
Ichiyama, Kenji
Yoshida, Ryoko
Hashimoto, Masayuki
Takimoto, Tomohito
Tanaka, Kentaro
Chinen, Takatoshi
Shichita, Takashi
Wyss-Coray, Tony
Sato, Katsuaki
Yoshimura, Akihiko
机构
[1] Kyushu Univ, Med Inst Bioregulat, Div Mol & Cellular Immunol, Higashi Ku, Fukuoka 8128582, Japan
[2] RIKEN Yokohama Inst, Lab Dentrit Cell Immunobiol, Res Ctr Allerg & Immunol, Yokohama, Kanagawa, Japan
[3] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA
关键词
D O I
10.4049/jimmunol.179.4.2170
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Dendritic cells (DCs) induce immunity and immunological tolerance as APCs. It has been shown that DCs secreting IL-10 induce IL-10(+) TrI-type regulatory T (Treg) cells, whereas Foxp3-positive Treg cells are expanded from naive CD4(+) T cells by coculturing with mature Ms. However, the regulatory mechanism of expansion of Foxp3(+) Treg cells by DCs has not been clarified. In this study, we demonstrated that suppressors of cytokine signaling (SOCS)-3-deficient DCs have a strong potential as Foxp3(+) T cell-inducing tolerogenic Ms. SOCS3(-/-) DCs expressed lower levels of class 11 MHC, CD40, CD86, and IL-12 than wild-type(WT)-DCs both in vitro and in vivo, and showed constitutive activation of STAT3. Foxp3(-) effector T cells were predominantly expanded by the priming with WT-DCs, whereas Foxp3(+) Treg cells were selectively expanded by SOCS3(-/-) DCs. Adoptive transfer of SOCS3(-/-) DCs reduced the severity of experimental autoimmune encephalomyelitis. Foxp3(+) T cell expansion was blocked by anti-TGF-beta Ab, and SOCS3(-/-) DCs produced higher levels of TGF-beta than WT-DCs, suggesting that TGF-beta plays an essential role in the expansion of Foxp3(+) Treg cells. These results indicate an important role of SOCS3 in determining on immunity or tolerance by Ms.
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页码:2170 / 2179
页数:10
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