Suppressor of Cytokine Signaling-1 Is Essential for Suppressing Dendritic Cell Activation and Systemic Autoimmunity
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 and interleukin-4. To define the...
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Veröffentlicht in: | Immunity (Cambridge, Mass.) Mass.), 2003-09, Vol.19 (3), p.437-450 |
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Sprache: | eng |
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Zusammenfassung: | 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 and interleukin-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 on a SOCS1
−/− background. In these mice, DCs were accumulated in the thymus and spleen and produced high levels of BAFF/BLyS and APRIL, resulting in the aberrant expansion of B cells and autoreactive antibody production. SOCS1-deficient DCs efficiently stimulated B cell proliferation in vitro and autoantibody production in vivo. These results indicate that SOCS1 plays an essential role in the normal DC functions and suppression of systemic autoimmunity. |
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ISSN: | 1074-7613 1097-4180 |
DOI: | 10.1016/S1074-7613(03)00240-1 |