Dissection of signaling cascades through gp130 in vivo: Reciprocal roles for STAT3- and SHP2-mediated signals in immune responses

Takuya Ohtani, Katsuhiko Ishihara, Toru Atsumi, Keigo Nishida, Yukiko Kaneko, Takaki Miyata, Shousaku Itoh, Masahiro Narimatsu, Hisoka Maeda, Toshiyuki Fukada, Motoyuki Itoh, Hideyuki Okano, Masahiko Hibi, Toshio Hirano

研究成果: Article

179 引用 (Scopus)

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We generated a series of knockin mouse lines, in which the cytokine receptor gp130-dependent STAT3 and/or SHP2 signals were disrupted, by replacing the mouse gp130 gene with human gp130 mutant cDNAs. The SHP2 signal-deficient mice (gp130(F759/F759)) were born normal but displayed splenomegaly and lymphadenopathy and an enhanced acute phase reaction. In contrast, the STAT3 signal-deficient mice (gp130(FXXQ/FXXQ)) died perinatally, like the gp130-deficient mice (gp130(D/D)). The gp13(F759/F759) mice showed prolonged gp130-induced STAT3 activation, indicating a negative regulatory role for SHP2. Th1 -type cytokine production and IgG2a and IgG2b production were increased in the gp13(F759/F759) mice, while they were decreased in the gp130(FXXQ/FXXQ) immune system. These results indicate that the balance of positive and negative signals generated through gp130 regulates the immune responses.

元の言語English
ページ(範囲)95-105
ページ数11
ジャーナルImmunity
12
発行部数1
DOI
出版物ステータスPublished - 2000 1
外部発表Yes

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

これを引用

Ohtani, T., Ishihara, K., Atsumi, T., Nishida, K., Kaneko, Y., Miyata, T., Itoh, S., Narimatsu, M., Maeda, H., Fukada, T., Itoh, M., Okano, H., Hibi, M., & Hirano, T. (2000). Dissection of signaling cascades through gp130 in vivo: Reciprocal roles for STAT3- and SHP2-mediated signals in immune responses. Immunity, 12(1), 95-105. https://doi.org/10.1016/S1074-7613(00)80162-4