Induction of hyper Th1 cell-type immune responses by dendritic cells lacking the suppressor of cytokine signaling-1 gene

Toshikatsu Hanada, Kentaro Tanaka, Yumiko Matsumura, Moriyasu Yamauchi, Hitomi Nishinakamura, Hiroyuki Aburatani, Ryuichi Mashima, Masato Kubo, Takashi Kobayashi, Akihiko Yoshimura

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79 Citations (Scopus)

Abstract

Suppressor of cytokine signaling (SOCS1/JAB) has been shown to play an important role in regulating dendritic cell (DC) function and suppressing inlammatory diseases and systemic autoimmunity. However, role of SOCS1 in DCs for the initiation of Th cell response has not been clarified. Here we demonstrate that SOCS1-deficient DCs induce stronger Th1-type responses both in vitro and in vivo. SOCS1-deficient DCs induced higher IFN-γ production from naive T cells than wild-type (WT) DCs in vitro. Lymph node T cells also produced a higher amount of IFN-γ when SOCS1-deficient bone marrow-derived DCs (BMDCs) were transferred in vivo. Moreover, SOCS1-/- BMDCs raised more effective anti-tumor immunity than WT BMDCs. Microarray analysis revealed that IFN-inducible genes were highly expressed in SOCS1-deficient DCs without IFN stimulation, suggesting hyper STAT1 activation in SOCS1 -/- DCs. These phenotypes of SOCS1-deicient DCs were similar to those of CD8α+ DCs, and in the WT spleen, SOCS1 is expressed at higher levels in the Th2-inducing CD4+ DC subset, relative to the Th1-inducing CD8α+ DC subset. We propose that reduction of the SOCS1 gene expression in DCs leads to CD8α+ DC-like phenotype which promotes Th1-type hyperresponses.

Original languageEnglish
Pages (from-to)4325-4332
Number of pages8
JournalJournal of Immunology
Volume174
Issue number7
DOIs
Publication statusPublished - Apr 1 2005

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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