Forced expression of stabilized c-Fos in dendritic cells reduces cytokine production and immune responses in vivo

Ryoko Yoshida, Mayu Suzuki, Ryota Sakaguchi, Eiichi Hasegawa, Akihiro Kimura, Takashi Shichita, Takashi Sekiya, Hiroshi Shiraishi, Kouji Shimoda, Akihiko Yoshimura

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Intracellular cyclic adenosine monophosphate (cAMP) suppresses innate immunity by inhibiting proinflammatory cytokine production by monocytic cells. We have shown that the transcription factor c-Fos is responsible for cAMP-mediated suppression of inflammatory cytokine production, and that c-Fos protein is stabilized by IKKβ-mediated phosphorylation. We found that S308 is one of the major phosphorylation sites, and that the S308D mutation prolongs c-Fos halflife. To investigate the role of stabilized c-Fos protein in dendritic cells (DCs) in vivo, we generated CD11c-promoter-deriven c-FosS308D transgenic mice. As expected, bone marrow-derived DCs (BMDCs) from these Tg mice produced smaller amounts of inflammatory cytokines, including TNF-α, IL-12, and IL-23, but higher levels of IL-10, in response to LPS, than those from wild-type (Wt) mice. When T cells were co-cultured with BMDCs from Tg mice, production of Th1 and Th17 cytokines was reduced, although T cell proliferation was not affected. Tg mice demonstrated more resistance to experimental autoimmune encephalomyelitis (EAE) than did Wt mice. These data suggest that c-Fos in DCs plays a suppressive role in certain innate and adaptive immune responses.

Original languageEnglish
Pages (from-to)247-252
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume423
Issue number2
DOIs
Publication statusPublished - Jun 29 2012
Externally publishedYes

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Dendritic Cells
Cytokines
Proto-Oncogene Proteins c-fos
Phosphorylation
T-cells
Cyclic AMP
Bone
Innate Immunity
Interleukin-23
Bone Marrow
Cell proliferation
T-Lymphocytes
Interleukin-12
Interleukin-10
Autoimmune Experimental Encephalomyelitis
Adaptive Immunity
Transcription Factors
Transgenic Mice
Half-Life
Cell Proliferation

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Forced expression of stabilized c-Fos in dendritic cells reduces cytokine production and immune responses in vivo. / Yoshida, Ryoko; Suzuki, Mayu; Sakaguchi, Ryota; Hasegawa, Eiichi; Kimura, Akihiro; Shichita, Takashi; Sekiya, Takashi; Shiraishi, Hiroshi; Shimoda, Kouji; Yoshimura, Akihiko.

In: Biochemical and Biophysical Research Communications, Vol. 423, No. 2, 29.06.2012, p. 247-252.

Research output: Contribution to journalArticle

Yoshida, R, Suzuki, M, Sakaguchi, R, Hasegawa, E, Kimura, A, Shichita, T, Sekiya, T, Shiraishi, H, Shimoda, K & Yoshimura, A 2012, 'Forced expression of stabilized c-Fos in dendritic cells reduces cytokine production and immune responses in vivo', Biochemical and Biophysical Research Communications, vol. 423, no. 2, pp. 247-252. https://doi.org/10.1016/j.bbrc.2012.05.097
Yoshida, Ryoko ; Suzuki, Mayu ; Sakaguchi, Ryota ; Hasegawa, Eiichi ; Kimura, Akihiro ; Shichita, Takashi ; Sekiya, Takashi ; Shiraishi, Hiroshi ; Shimoda, Kouji ; Yoshimura, Akihiko. / Forced expression of stabilized c-Fos in dendritic cells reduces cytokine production and immune responses in vivo. In: Biochemical and Biophysical Research Communications. 2012 ; Vol. 423, No. 2. pp. 247-252.
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