Title

Aim2 Deficiency in Mice Suppresses the Expression of the Inhibitory Fc{gamma} Receptor (Fc{gamma}RIIB) through the Induction of the IFN-Inducible p202, a Lupus Susceptibility Protein

UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology

Date

6-15-2011

Document Type

Article

Subjects

Intracellular Signaling Peptides and Proteins; Receptors, IgG; Nuclear Proteins

Abstract

Murine Aim2 and Ifi202 genes (encoding for the Aim2 and p202 proteins) are members of the IFN-inducible Ifi200 gene family. The Aim2 deficiency in mice activates IFN signaling and stimulates the expression of the lupus susceptibility gene, the Ifi202, located within the NZB autoimmunity 2 (Nba2) interval. Given that the deficiency in the expression of the Fcgr2b gene (encoding for the inhibitory FcgammaRIIB receptor) is associated with increased lupus susceptibility in mice, we investigated whether the Aim2 protein could regulate the expression of Fcgr2b gene. In this article, we report that Aim2 deficiency in mice suppresses the expression of the FcgammaRIIB receptor. Interestingly, the Fcgr2b-deficient cells expressed increased levels of the IFN-beta, activated IFN signaling, and expressed reduced levels of the Aim2 protein. Treatment of splenic cells with IFN-alpha or -gamma reduced levels of the FcgammaRIIB mRNA and protein and also decreased the activity of the FcgammaRIIB p(-729/+585) Luc reporter. Moreover, levels of the FcgammaRIIB receptor were significantly higher in the Stat1-deficient splenic cells than in the wild-type cells. Accordingly, increased expression of IFN-beta in lupus-prone B6.Nba2-ABC mice, as compared with non-lupus-prone C57BL/6 (B6) or B6.Nba2-C mice, was associated with reduced expression of the FcgammaRIIB receptor. Notably, overexpression of the p202 protein in cells decreased the expression of the Aim2 gene, activated the IFN response, and suppressed the expression of the Fcgr2b gene. These observations demonstrate that the expression of Aim2 protein is required to maintain the expression of the Fcgr2b gene and also predict epistatic interactions between the Ifi200 genes and the Fcgr2b gene within the Nba2 interval.

Rights and Permissions

Citation: J Immunol. 2011 Jun 15;186(12):6762-70. Epub 2011 May 6. Link to article on publisher's site

Related Resources

Link to Article in PubMed

PubMed ID

21551362