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

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Abstract

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.

Original languageEnglish
Pages (from-to)2170-2179
Number of pages10
JournalJournal of Immunology
Volume179
Issue number4
DOIs
Publication statusPublished - 2007 Aug 15

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Matsumura, Y., Kobayashi, T., Ichiyama, K., Yoshida, R., Hashimoto, M., Takimoto, T., Tanaka, K., Chinen, T., Shichita, T., Wyss-Coray, T., Sato, K., & Yoshimura, A. (2007). Selective expansion of Foxp3-positive regulatory T cells and immunosuppression by suppressors of cytokine signaling 3-deficient dendritic cells. Journal of Immunology, 179(4), 2170-2179. https://doi.org/10.4049/jimmunol.179.4.2170