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

Research output: Contribution to journalArticle

182 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)95-105
Number of pages11
JournalImmunity
Volume12
Issue number1
DOIs
Publication statusPublished - 2000 Jan
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    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