Rig-I-/- mice develop colitis associated with downregulation of G alpha i2.
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 naive 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 alpha i2 subunit (G alpha i2) 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 G alpha i2 expression. Moreover, G alpha i2 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 G alpha i2 expression and T-cell activation. The development of colitis may be, at least in part, associated with downregulation of G alpha i2 and disturbed T-cell homeostasis.
Wang
Yi
Y
Department of Medical Genetics, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Zhang
Hong-Xin
HX
Sun
Yue-Ping
YP
Liu
Zi-Xing
ZX
Liu
Xue-Song
XS
Wang
Long
L
Lu
Shun-Yuan
SY
Kong
Hui
H
Liu
Qiao-Ling
QL
Li
Xi-Hua
XH
Lu
Zhen-Yu
ZY
Chen
Sai-Juan
SJ
Chen
Zhu
Z
Bao
Shi-San
SS
Dai
Wei
W
Wang
Zhu-Gang
ZG
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D016264:Dextran Sulfate / Q000633:toxicity; D051960:GTP-Binding Protein alpha Subunit, Gi2 / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism
D016264:Dextran Sulfate; C503356:Ddx58 protein, mouse; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D051960:GTP-Binding Protein alpha Subunit, Gi2