Suppressor of cytokine signaling-1 is essential for suppressing dendritic cell activation and systemic autoimmunity

Toshikatsu Hanada, Hiroki Yoshida, Seiya Kato, Kentaro Tanaka, Kohsuke Masutani, Jun Tsukada, Yoshio Nomura, Hiromitsu Mimata, Masato Kubo, Akihiko Yoshimura

Research output: Contribution to journalArticle

181 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)437-450
Number of pages14
JournalImmunity
Volume19
Issue number3
DOIs
Publication statusPublished - 2003 Sep 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Hanada, T., Yoshida, H., Kato, S., Tanaka, K., Masutani, K., Tsukada, J., Nomura, Y., Mimata, H., Kubo, M., & Yoshimura, A. (2003). Suppressor of cytokine signaling-1 is essential for suppressing dendritic cell activation and systemic autoimmunity. Immunity, 19(3), 437-450. https://doi.org/10.1016/S1074-7613(03)00240-1