The suppressor of cytokine signaling-1 (SOCS1/JAB) negatively regulates not only the cytokine-signaling pathway, but also lipopolysaccharide (LPS)-induced macrophage activation. We found that SOCS1-deficient dendritic cells (DCs) were also hyperresponsive to interferon-γ (IFNγ) and interleukin-4 (IL-4). To define the role of SOCS1-deficient DCs in vivo, we generated mice in which the SOCS1 expression was restored in T and B cells under a SOCS1 -/- background. In these mice, DCs were accumulated in the thymus and spleen and produced high levels of BAFF/BLyS, resulting in the aberrant expansion of B cells and autoreactive antibody production. SOCS1-deficient DCs efficiently stimulated B cell proliferation in vitro and auto-antibody production in vivo. These results indicate that SOCS1 plays an essential role in the normal DC functions and in the suppression of systemic autoimmunity.
|Number of pages||8|
|Journal||Nishinihon Journal of Urology|
|Publication status||Published - 2005 Apr 1|
- Autoimmune diseases
- Dendritic cell
- Signal transduction
ASJC Scopus subject areas