Interferon-inducible Ifi200-family genes in systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is the prototype of complex autoimmune diseases. Studies have suggested that genetic, hormonal, and environmental factors contribute to the development of the disease. Interestingly, several recent studies involving SLE patients and mouse models of the disease have suggested a role for interferon (IFN)-stimulated genes (ISGs) in the development of SLE. One family of ISGs is the Ifi200-family, which includes mouse (Ifi202a, Ifi202b, Ifi203, Ifi204, and Ifi205) and human (IFI16, MNDA, AIM2, and IFIX) genes. The mouse genes cluster between serum amyloid P-component (Apcs) and alpha-spectrin (Spna-1) genes on chromosome 1 and the human genes cluster in syntenic region 1q23. The Ifi200-family genes encode structurally and functionally related proteins (the p200-family proteins). Increased expression of certain p200-family proteins in cells is associated with inhibition of cell proliferation, modulation of apoptosis, and cell differentiation. Our studies involving generation of B6.Nba2 congenic mice, coupled with gene expression analyses, identified the Ifi202 as a candidate lupus-susceptibility gene. Importantly, recent studies using different mouse models of SLE have suggested that increased expression of Ifi202 gene (encoding p202 protein) in immune cells contributes to lupus susceptibility. Consistent with a functional role for the p202 protein in lupus susceptibility, increased levels of IFI16 protein in human SLE patients are associated with the diseases. This review summarizes recent findings concerning the regulation and role of p200-family proteins in the development of SLE.
Choubey
Divaker
D
Department of Environmental Health, University of Cincinnati, 3223 Eden Avenue, P.O. Box 670056, Cincinnati, OH 45267, United States. Divaker.choubey@uc.edu
Panchanathan
Ravichandran
R
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D025461:Feedback, Physiological / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics* / Q000276:immunology; D010750:Phosphoproteins / Q000235:genetics* / Q000276:immunology; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000276:immunology; D012737:Sex Factors; D015533:Transcriptional Activation / Q000276:immunology
C092537:Ifi202b protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; C076700:IFI16 protein, human