TY - JOUR
T1 - Suppressor of cytokine signaling-1 is essential for suppressing dendritic cell activation and systemic autoimmunity
AU - Hanada, Toshikatsu
AU - Yoshida, Hiroki
AU - Kato, Seiya
AU - Tanaka, Kentaro
AU - Masutani, Kohsuke
AU - Tsukada, Jun
AU - Nomura, Yoshio
AU - Mimata, Hiromitsu
AU - Kubo, Masato
AU - Yoshimura, Akihiko
N1 - Funding Information:
We thank Ms. Y. Kawabata for technical assistance, Ms. M. Ohara for language assistance, Dr. T. Naka for discussion and comments, and Ms. N. Arifuku for manuscript preparation. This work was supported by Special Grants-in-Aid from the Ministry of Education, Science, Technology, Sports, and Culture of Japan, the Japan Health Science Foundation, the Human Frontier Science Program, the Japan Research Foundation for Clinical Pharmacology, and Uehara Memorial Foundation.
PY - 2003/9/1
Y1 - 2003/9/1
N2 - 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.
AB - 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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U2 - 10.1016/S1074-7613(03)00240-1
DO - 10.1016/S1074-7613(03)00240-1
M3 - Article
C2 - 14499118
AN - SCOPUS:10744223505
SN - 1074-7613
VL - 19
SP - 437
EP - 450
JO - Immunity
JF - Immunity
IS - 3
ER -
