| First Author | Yoshida R | Year | 2012 |
| Journal | Biochem Biophys Res Commun | Volume | 423 |
| Issue | 2 | Pages | 247-52 |
| PubMed ID | 22634314 | Mgi Jnum | J:185355 |
| Mgi Id | MGI:5428350 | Doi | 10.1016/j.bbrc.2012.05.097 |
| Citation | Yoshida R, et al. (2012) Forced expression of stabilized c-Fos in dendritic cells reduces cytokine production and immune responses in vivo. Biochem Biophys Res Commun 423(2):247-52 |
| abstractText | 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 IKKbeta-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-alpha, 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. |
