Volume 17, No 10, Oct 2007

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 17 Issue 10, October 2007: 858-868

ORIGINAL ARTICLES

Rig-I^-/- mice develop colitis associated with downregulation of Gαi2

Yi Wang^1,*, Hong-Xin Zhang^1,*, Yue-Ping Sun¹, Zi-Xing Liu¹, Xue-Song Liu¹, Long Wang^2,3, Shun-Yuan Lu^2,3, Hui Kong³, Qiao-Ling Liu³, Xi-Hua Li¹, Zhen-Yu Lu¹, Sai-Juan Chen², Zhu Chen², Shi-San Bao⁴, Wei Dai⁵ and Zhu-Gang Wang^1,2,3,4

¹Department of Medical Genetics, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

²State Key Laboratory of Medical Genomics, Rui-Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

³Shanghai Research Center for Model Organisms, Shanghai 201203, China

⁴Department of Pathology, University of Sydney, Sydney, 2570 NSW, Australia

⁵Department of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA Correspondence: Zhu-Gang Wang(zhugangw@shsmu.edu.cn)

RIG-I (retinoid acid-inducible gene-I), a putative RNA helicase with a cytoplasmic caspase-recruitment domain (CARD), was identified as a pattern-recognition receptor (PRR) that mediates antiviral immunity by inducing type I interferon production. To further study the biological function of RIG-I, we generated Rig-I^-/- mice through homologous recombination, taking a different strategy to the previously reported strategy. Our Rig-I^-/- mice are viable and fertile. Histological analysis shows that Rig-I^-/- mice develop a colitis-like phenotype and increased susceptibility to dextran sulfate sodium-induced colitis. Accordingly, the size and number of Peyer's patches dramatically decreased in mutant mice. The peripheral T-cell subsets in mutant mice are characterized by an increase in effector T cells and a decrease in naïve T cells, indicating an important role for Rig-I in the regulation of T-cell activation. It was further found that Rig-I deficiency leads to the downregulation of G protein αi2 subunit (Gαi2) in various tissues, including T and B lymphocytes. By contrast, upregulation of Rig-I in NB4 cells that are treated with ATRA is accompanied by elevated Gαi2 expression. Moreover, Gαi2 promoter activity is increased in co-transfected NIH3T3 cells in a Rig-I dose-dependent manner. All these findings suggest that Rig-I has crucial roles in the regulation of Gαi2 expression and T-cell activation. The development of colitis may be, at least in part, associated with downregulation of Gαi2 and disturbed T-cell homeostasis.

Cell Research (2007) 17:858-868. doi: 10.1038/cr.2007.81; published online 25 September 2007

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