TY - JOUR
T1 - Dissection of signaling cascades through gp130 in vivo
T2 - Reciprocal roles for STAT3- and SHP2-mediated signals in immune responses
AU - Ohtani, Takuya
AU - Ishihara, Katsuhiko
AU - Atsumi, Toru
AU - Nishida, Keigo
AU - Kaneko, Yukiko
AU - Miyata, Takaki
AU - Itoh, Shousaku
AU - Narimatsu, Masahiro
AU - Maeda, Hisoka
AU - Fukada, Toshiyuki
AU - Itoh, Motoyuki
AU - Okano, Hideyuki
AU - Hibi, Masahiko
AU - Hirano, Toshio
N1 - Funding Information:
We thank Dr. K. Yasukawa (Tosoh) and Dr. M. Saito for providing reagents. We thank Ms. R. Masuda, Ms. A. Kubota, and Ms. T. Kimura for secretarial and Ms. K. Nishikawa-Hirata and Ms. J. Ishikawa for excellent technical assistance. This work was supported by grants and a Grant-in-Aid for COE Research from the Ministry of Education, Science, Sports, and Culture in Japan and grants from the Searle Scientific Research Fellowship and the Osaka Foundation for the Promotion of Clinical Immunology. T. O., M. I., M. N., and T. F. are Research Fellows of the Japan Society for the Promotion of Science.
PY - 2000/1
Y1 - 2000/1
N2 - 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.
AB - 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.
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U2 - 10.1016/S1074-7613(00)80162-4
DO - 10.1016/S1074-7613(00)80162-4
M3 - Article
C2 - 10661409
AN - SCOPUS:0001903105
SN - 1074-7613
VL - 12
SP - 95
EP - 105
JO - Immunity
JF - Immunity
IS - 1
ER -
