Mice that lack activity of αvβ6-and αvβ8-integrins reproduce the abnormalities of Tgfb1- and Tgfb3-null mice

被引:176
作者
Aluwihare, Poshala [1 ]
Mu, Zhenyu [1 ]
Zhao, Zhicheng [1 ]
Yu, Dawen [1 ]
Weinreb, Paul H. [2 ]
Horan, Gerald S. [2 ]
Violette, Shelia M. [2 ]
Munger, John S. [1 ]
机构
[1] NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA
[2] Biogen Inc, Cambridge, MA 02142 USA
关键词
Autoimmunity; Integrins; Langerhans cells; Palate fusion; TGFb; GROWTH-FACTOR-BETA; INTEGRIN-MEDIATED ACTIVATION; TRANSFORMING GROWTH-FACTOR-BETA-1; TARGETED DISRUPTION; FOXP3; EXPRESSION; T-CELLS; HOMEOSTASIS; TGF-BETA-1; INFLAMMATION; MOUSE;
D O I
10.1242/jcs.035246
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The arginine-glycine-aspartate (RGD)-binding integrins alpha v beta 6 and alpha v beta 8 activate latent TGF beta 1 and TGF beta 3 in vivo, but it is uncertain whether other RGD-binding integrins such as integrins alpha v beta 5 and alpha v beta 3 activate these TGF beta isoforms. To define the combined role of alpha v beta 6- and alpha v beta 8-integrin in TGF beta activation, we analyzed mice lacking function of both integrins by means of gene deletion and/or pharmacologic inhibition. Most Itgb6(-/-); Itgb8(-/-) embryos die at mid-gestation; those that survive develop cleft palate - as observed in Tgfb3(-/-) mice. Itgb8(-/-) mice treated with an anti-alpha v beta 6-integrin antibody develop severe autoimmunity and lack Langerhans cells - similar to Tgfb1-null mice. These results support a model in which TGF beta 3-mediated palate fusion and TGF beta 1-mediated suppression of autoimmunity and generation of Langerhans cells require integrins alpha v beta 6 and alpha v beta 8 but not other RGD-binding integrins as TGF beta activators.
引用
收藏
页码:227 / 232
页数:6
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