Interferon-inducible p200-family proteins as novel sensors of cytoplasmic DNA: role in inflammation and autoimmunity.
Deregulated innate immune responses that result in increased levels of type I interferons (IFNs) and stimulation of IFN-inducible genes are thought to contribute to chronic inflammation and autoimmunity. One family of IFN-inducible genes is the Ifi200 family, which includes the murine (eg, Ifi202a, Ifi202b, Ifi203, Ifi204, Mndal, and Aim2) and human (eg, IFI16, MNDA, IFIX, and AIM2) genes. Genes in the family encode structurally related proteins (the p200-family proteins), which share at least one partially conserved repeat of 200-amino acid (200-AA) residues. Consistent with the presence of 2 consecutive oligonucleotide/oligosaccharide-binding folds in the repeat, the p200-family proteins can bind to DNA. Additionally, these proteins (except the p202 proteins) also contain a pyrin (PYD) domain in the N-terminus. Increased expression of p202 proteins in certain strains of female mice is associated with lupus-like disease. Interestingly, only the Aim2 protein is conserved between the mouse and humans. Several recent studies have provided evidence that the Aim2 and p202 proteins can recognize DNA in cytoplasm and the Aim2 protein upon sensing DNA can form a caspase-1-activating inflammasome. In this review, we discuss how the ability of p200-family proteins to sense cytoplasmic DNA may contribute to the development of chronic inflammation and associated diseases.
Choubey
Divaker
D
Department of Environmental Health, University of Cincinnati, Cincinnati, Ohio 45267, USA. Divaker.choubey@uc.edu
Duan
Xin
X
Dickerson
Eric
E
Ponomareva
Larissa
L
Panchanathan
Ravichandran
R
Shen
Hui
H
Srivastava
Ratika
R
D000818:Animals; D015551:Autoimmunity; D004268:DNA-Binding Proteins / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007249:Inflammation; D051379:Mice; D009687:Nuclear Proteins / Q000276:immunology*
C410167:AIM2 protein, human; D004268:DNA-Binding Proteins; C101635:HIN-200 protein, human; D009687:Nuclear Proteins