Interferon-inducible Ifi200-family genes in systemic lupus erythematosus

Abstract

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 α-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.

The emerging role of human PYHIN proteins in innate immunity: Implications for health and disease

“…Genetic factors are also thought to be important in determining disease risk, for example, PYHIN proteins have been reported to lie within a susceptibility locus for systemic lupus erythematosus (SLE) [59] and the PYHIN1 locus has been identified as a novel susceptibility locus for asthma, specifically for individuals of African descent [60].…”

Interferon-inducible Ifi202b gene in (NZB × NZW)F1 lupus-prone mice

“…2 Moreover, both Ifi202a and Ifi202b genes are co-expressed in mouse organs and in immune cells. 2,3 The p202a and p202b proteins differ by seven amino acids residues (out of 445 residues) in the N-terminus. 2 These minor differences in the amino acids residues between p202a and p202b proteins could account for the lack of a phenotype in the Ifi202a knockout mice.…”

“…3,4 Moreover, these antibodies cross-react with other proteins. 4 Given that the authors do not provide any details concerning the p202 antibodies that they used (purchased from Santa Cruz Biotechnology, Santa Cruz, CA, USA), and their experiments do not include appropriate controls to demonstrate the specificity of p202 antibodies, therefore, the identity of the protein band that authors detected remains unclear.…”

The Duality of AIM2 Inflammasome: A Focus on its Role in Autoimmunity and Skin Diseases

“…Collectively these studies provide insights into the function of AIM2 as tumor suppressor, especially in colorectal cancer. However, as discussed above, AIM2 inflammasome dysregulation, in terms of incorrect recognition of cytoplasmic self-DNA is reported to result in auto-inflammatory and auto-immune diseases (Smith and Jefferies, 2014;Choubey and Panchanathan, 2008).…”

“…The presence of altered self-DNA may be sensed in the nuclear compartment of cells, leading to inflammation and auto-immune responses (Choubey and Panchanathan, 2008;Fish, 2008). Systemic autoimmune diseases include Sjogren's Syndrome (SS), Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA) and Systemic Sclerosis (SSc) (Choubey and Panchanathan, 2008).…”