Overlapping and distinct roles of STAT4 and T-bet in the regulation of T cell differentiation and allergic airway inflammation

被引：18

作者：

Furuta, Shunsuke ^{[2
,3
]}

Kagami, Shin-ichiro ^{[1
,3
]}

Tamachi, Tomohiro ^{[3
]}

Ikeda, Kei ^{[3
]}

Fujiwara, Michio ^{[3
]}

Suto, Akira ^{[1
,3
]}

Hirose, Koichi ^{[3
]}

Watanabe, Norihiko ^{[3
]}

Saito, Yasushi ^{[2
]}

Iwamoto, Itsuo ^{[4
]}

Nakajima, Hiroshi ^{[1
,3
]}

机构：

[1] Chiba Univ, Grad Sch Med, Dept Mol Genet, Chiba 2608670, Japan

[2] Chiba Univ, Grad Sch Med, Dept Clin Cell Biol, Chiba 2608670, Japan

[3] Chiba Univ Hosp, Dept Allergy & Clin Immunol, Chiba, Japan

[4] Asahi Gen Hosp, Res Ctr Allergy & Clin Immunol, Chiba, Japan

来源：

JOURNAL OF IMMUNOLOGY | 2008年 / 180卷 / 10期

关键词：

D O I：

10.4049/jimmunol.180.10.6656

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

T-bet and STAT4 play critical roles in helper T cell differentiation, especially for Th1 cells. However, it is still unknown about the relative importance and redundancy of T-bet and STAT4 for Th1 differentiation. It is also unknown about their independent role of T-bet and STAT4 in the regulation of allergic airway inflammation. In this study, we addressed these issues by comparing T-bet-deficient (T-bet(-/-)) mice, STAT4(-/-) mice, and T-bet- and STAT4-double-deficient (T-bet(-/-)STAT4(-/-)) mice on the same genetic background. Th1 differentiation was severely decreased in T-bet(-/-) mice and STAT4(-/-) mice as compared with that in wild-type mice, but Th1 differentiation was still observed in T-bet(-/-) mice and STAT4(-/-) mice. However, Th1 cells were hardly detected in T-bet(-/-)STAT4(-/-) mice. In contrast, the maintenance of Th17 cells was enhanced in T-bet(-/-) mice but was reduced in STAT4(-/-) mice and T-bet(-/-)STAT4(-/-) mice. In vivo, Ag-induced eosinophil and neutrophil recruitment into the airways was enhanced in T-bet(-/-) mice but was attenuated in STAT4(-/-) mice and T-bet(-/-)STAT4(-/-) mice. Ag-induced IL-17 production in the airways was also diminished in STAT4(-/-) mice and T-bet(-/-)STAT4(-/-) mice. These results indicate that STAT4 not only plays an indispensable role in T-bet-independent Th1 differentiation but also is involved in the maintenance of Th17 cells and the enhancement of allergic airway inflammation.

引用

页码：6656 / 6662

页数：7

共 36 条

[1] T-bet is a STAT1-induced regulator of IL-12R expression in naive CD4+ T cells [J].