Stimulation of T cells up-regulates expression of Ifi202, an interferon-inducible lupus susceptibility gene, through activation of JNK/c-Jun pathway

Chen, Jianming; Panchanathan, Ravichandran; Choubey, Divaker

doi:10.1016/j.imlet.2008.02.005

Cited by 11 publications

(11 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Likewise, we recently noted [68] that stimulation of splenic T cells in vitro with anti-CD3 and anti-CD28 up-regulates the expression of the Ifi202 gene. Furthermore, generation of B6.Nba2 mice that were defective in type I IFN-signaling revealed that the defect resulted in only two fold reduction in Ifi202 mRNA levels in splenocytes as compared to the wild type mice [30].…”

Section: Regulation Of Ifi202 Expressionmentioning

confidence: 71%

Interferon-inducible Ifi200-family genes in systemic lupus erythematosus

2008

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Regulation Of Ifi202 Expressionmentioning

confidence: 71%

Interferon-inducible Ifi200-family genes in systemic lupus erythematosus

2008

Self Cite

View full text Add to dashboard Cite

show abstract

“…Stimulation of splenic T cells from the NZB female mice by anti-CD3 and anti-CD28 up-regulates the expression of Ifi202 gene (Chen et al, 2008). Therefore, we investigated whether stimulation of splenic T or B cells regulates the expression of Aim2 gene.…”

Section: Resultsmentioning

confidence: 99%

“…Purified splenic T cells were stimulated as described previously (Chen et al 2008). In brief, freshly isolated splenic cells (2–4 ×10 6 ) were plated in 60 mm plastic cell culture plates either coated with purified hamster anti-mouse CD3 epsilon (10 μg/plate; from eBioscience, San Diego, CA) antibody or purified golden Syrian hamster IgG (5 μg/plate; from eBioscience) isotype control antibody.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Cell type and gender-dependent differential regulation of the p202 and Aim2 proteins: Implications for the regulation of innate immune responses in SLE

Panchanathan

Duan

Arumugam

et al. 2011

Molecular Immunology

Self Cite

View full text Add to dashboard Cite

Upon sensing cytosolic double-stranded DNA (dsDNA), the murine Aim2 (encoded by the Aim2 gene) protein forms an inflammasome and promotes the secretion of proinflammatory cytokines, such as IL-1β and IL-18. In contrast, the p202 protein (encoded by the Ifi202 gene) does not form an inflammasome. Previously, we have reported that the interferon (IFN) and female sex hormone-induced increased nuclear levels of p202 protein in immune cells are associated with increased susceptibility to develop a lupus-like disease. However, signaling pathways that regulate the expression of Aim2 protein remain unknown. Here we report that the expression of Aim2 gene is induced in bone marrow-derived macrophages (BMDMs) by IFN-α treatment and the expression is, in part, STAT1-dependent. However, treatment of splenic T or B cells with IFN-α or their stimulation, which induced the expression of Ifi202 gene, did not induce the expression of Aim2 gene. Furthermore, treatment of cells with the male hormone androgen increased levels of Aim2 mRNA and protein. Moreover, treatment of murine macrophage cell lines (RAW264.7 and J774A.1) with IFN-α differentially induced the expression of Aim2 and p202 proteins and regulated their sub-cellular localization. Additionally, activation of Toll-like receptors (TLR3, 4, and 9) in BMDMs and cell lines also differentially regulated the expression of Aim2 and Ifi202 genes. Our observations demonstrate that cell type and gender-dependent factors differentially regulate the expression of the Aim2 and p202 proteins, thus, suggesting opposing roles for these two proteins in innate immune responses in lupus disease.

show abstract

“…[9][10][11]30 In the present study, the number of T cells increased in female BXSB/MpJ glomeruli. Chen et al 31 demonstrated that the stimulation of both a mouse T-cell hybridoma cell line (2B4.11) and T cells derived from lupus-prone NZB upregulate the Ifi202b expression, in part, through the JNK/c-Jun pathway. On the basis of these findings, we proposed that the close correlation between renal overexpression of Ifi202b and infiltrating inflammatory cells exacerbates the pathological condition of MPGN in female BXSB/MpJ mice similar to other lupus-prone mice.…”

Section: Discussionmentioning

confidence: 99%

BXSB-type genome causes murine autoimmune glomerulonephritis: pathological correlation between telomeric region of chromosome 1 and Yaa

et al. 2014

View full text Add to dashboard Cite

The autoimmune-prone BXSB/MpJ-Yaa mouse is a model of membranous proliferative glomerulonephritis (MPGN). Severe MPGN has been reported only in male BXSB/MpJ-Yaa mice because of the Y-linked autoimmune accelerator (Yaa) locus. However, we show that female BXSB/MpJ mice develop age-related MPGN without Yaa. Female BXSB/MpJ mice clearly developed MPGN characterized by increased mesangial cells, thickening of the glomerular basement membrane (GBM), double contouring and spike formation of GBM with T-cell infiltrations and podocyte injuries corresponding with increased autoantibody production and albuminuria. Analysis of the renal levels of the Fc gamma receptor (Fcgr) and interferon-activated gene 200 (Ifi200) family genes, which are MPGN candidate genes localized to the telomeric region of chromosome 1 (Chr.1), showed that Fcgr2b levels decreased, whereas Fcgr3 and Ifi202b levels increased in female BXSB/MpJ mice compared with healthy C57BL/6 mice. Furthermore, in isolated glomeruli, microarray analysis revealed that Fcgr3, Fcgr4 and Ifi202b expression was higher in male BXSB/MpJ-Yaa mice than in male BXSB/MpJ mice. These findings indicate that the BXSB/MpJ-type genome causes age-related MPGN with significant contribution from the telomeric region of Chr.1, and Yaa enhances the expression of genes localizing to this locus, thereby leading to severe MPGN in male mice.

show abstract

Stimulation of T cells up-regulates expression of Ifi202, an interferon-inducible lupus susceptibility gene, through activation of JNK/c-Jun pathway

Cited by 11 publications

References 48 publications

Interferon-inducible Ifi200-family genes in systemic lupus erythematosus

Interferon-inducible Ifi200-family genes in systemic lupus erythematosus

Cell type and gender-dependent differential regulation of the p202 and Aim2 proteins: Implications for the regulation of innate immune responses in SLE

BXSB-type genome causes murine autoimmune glomerulonephritis: pathological correlation between telomeric region of chromosome 1 and Yaa

Contact Info

Product

Resources

About