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

Yumiko Matsumura, Takashi Kobayashi, Kenji Ichiyama, Ryoko Yoshida, Masayuki Hashimoto, Tomohito Takimoto, Kentaro Tanaka, Takatoshi Chinen, Takashi Shichita, Tony Wyss-Coray, Katsuaki Sato, Akihiko Yoshimura

研究成果: ジャーナルへの寄稿学術誌査読

95 被引用数 (Scopus)

抄録

Dendritic cells (DCs) induce immunity and immunological tolerance as APCs. It has been shown that DCs secreting IL-10 induce IL-10+ Tr1-type regulatory T (Treg) cells, whereas Foxp3-positive Treg cells are expanded from naive CD4+ T cells by coculturing with mature DCs. 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 DCs. SOCS3-/- DCs expressed lower levels of class II 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-β Ab, and SOCS3-/- DCs produced higher levels of TGF-β than WT-DCs, suggesting that TGF-β 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 DCs.

本文言語英語
ページ(範囲)2170-2179
ページ数10
ジャーナルJournal of Immunology
179
4
DOI
出版ステータス出版済み - 8月 15 2007

!!!All Science Journal Classification (ASJC) codes

  • 免疫学

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