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- W2264992753 abstract "Immunity-related GTPases (IRG) are essential, interferon-inducible resistant factors in mice that are actively against a broad spectrum of important intracellular pathogens. IRGs are represented by 25 genes in the mouse and also in almost all mammals and many other vertebrates, but surprisingly not in human. Structurally IRGs all share canonical GTP-binding domains and the crystal structure of one representative family member, Irga6, possesses an H-Ras-1-like GTP-binding domain. The biochemical properties of Irga6 are reminiscent of dynamins. Though the resistance mechanisms are still obscure, there is growing evidence supporting the role of IRG proteins as cell-autonomous resistant factors most probably through their direct targeting to intracellular pathogen-containing membrane compartments. IRGs are expressed under the tight regulation of IFNs. We found in this work unexpectedly that IRG proteins do have significant constitutive as well as IFN-induced expression in vivo. In liver at least for one member of IRG, Irga6, this differential expression is achieved by alternative activation of a liver-specific promoter and an IFN-inducible promoter. The constitutively expressed Irga6 in the presence of other constitutively expressed IRG proteins in primary hepatocytes is able to launch a similar anti-T.gondii program as IFN-induced protein, implying the role of IRG proteins as sentinel in the resistance against intracellular pathogens in liver that is an organ of immune privilege. Peculiar Irga6 focal expression in liver as well as in kidney is also observed and proved to be induced by local production of IFNs. This production of IFN-γ that induces Irga6 focal expression in liver surprisingly represents the local activation of NKT cells even in the absence of microbial environment (germ-free mice). Even though the causes of this NKT cell activation are still elusive, we speculate that this stimulation of NKT cells may stand for an ongoing process required for the maintenance of the effector status for peripheral NKT cells." @default.
- W2264992753 created "2016-06-24" @default.
- W2264992753 creator A5051829015 @default.
- W2264992753 date "2007-01-01" @default.
- W2264992753 modified "2023-09-23" @default.
- W2264992753 title "Interferon-induced and Constitutive Expression of Immunity-related GTPases (IRG) in Mouse Tissues" @default.
- W2264992753 hasPublicationYear "2007" @default.
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