Table 1 |
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|
Epigenetic perturbations observed in lupus T cells |
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|
Gene/pathway |
Epigenetic defect |
Cell type |
Consequence |
Reference |
|
|
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|
ERK pathway |
Defective signaling |
Human and murine T cells |
Reduced DNMT1 expression and reduced T cell DNA methylation |
|
|
PRF1 |
Hypomethylation |
CD4+ T cells |
Increased perforin expression |
|
|
ITGAL |
Hypomethylation |
CD4+ T cells |
Increased CD11a expression |
|
|
CD40LG |
Hypomethylation |
CD4+ T cells |
B-cell hyperactivation |
[36] |
|
KIR2DL4 (KIR) |
Hypomethylation |
CD4+ T cells |
Increased KIR expression |
|
|
TNFSF7 |
Hypomethylation |
CD4+ T cells |
Increased CD70 expression |
|
|
GADD45A |
Overexpression |
CD4+ T cells |
Decreased DNA methylation |
[51] |
|
Folate biosynthesis |
Hypermethylation |
CD4+ T cells |
Impaired DNA methylation? |
[62] |
|
RUNX3 |
Hypermethylation |
CD4+ T cells |
Impaired T cell proliferation? |
[62] |
|
CD9 |
Hypomethylation |
CD4+ T cells |
Increased T cell activation? |
[62] |
|
MMP9 |
Hypomethylation |
CD4+ T cells |
? |
[62] |
|
PDGFRA |
Hypomethylation |
CD4+ T cells |
? |
[62] |
|
SOX5 |
Hypomethylation |
CD4+ T cells |
? |
[62] |
|
miR-126 |
Overexpression |
CD4+ T cells |
Downregulation of DNMT1 |
[79] |
|
miR-146 |
Underexpression |
CD4+ T cells; murine T splenocytes |
Increased type I IFN |
|
|
miR-17-92 |
Overexpression |
Murine T splenocytes |
Lymphocyte stability |
[68] |
|
miR-155 |
Overexpression |
CD4+ T cells; CD4+ CD25+ T cells |
Reduced Treg cell stability |
[90] |
|
miR-101a |
Overexpression |
Murine T splenocytes |
Reduced EZH2? |
[68] |
|
miR-31 |
Overexpression |
Regulatory T cells; murine T splenocytes |
Repression of FOXP3 |
|
|
miR-21 |
Overexpression |
CD4+ T cells |
Targets ERK pathway leading to lower DNMT1 |
[78] |
|
miR-125a |
Underexpression |
CD4+ T cells |
Targets KLF13 leading to increased RANTES |
[67] |
|
miR-148a |
Overexpression |
CD4+ T cells |
Downregulates DNMT1 |
[78] |
|
RFX1 |
Underexpression |
CD4+ T cells |
Reduced H3K9me3 and DNA methylation |
|
|
|
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|
CD40LG, CD40 ligand; DNMT, DNA methyltransferase; ERK, extracellular signal-regulated kinase; GADD45A, growth arrest and DNA-damage-inducible 45 alpha; H3K9me3, histone 3 lysine 9 trimethylation; KIR, killer immunoglobulin-like receptor; Treg, regulatory T cell. |
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|
Hughes and Sawalha Arthritis Research & Therapy 2011 13:245 doi:10.1186/ar3484 |
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