Table 1.
Epigenetic perturbations observed in lupus T cells
| Gene/pathway | Epigenetic defect | Cell type | Consequence | Reference |
|---|---|---|---|---|
| ERK pathway | Defective signaling | Human and murine T cells | Reduced DNMT1 expression and reduced T cell DNA methylation | [23,32] |
| PRF1 | Hypomethylation | CD4+ T cells | Increased perforin expression | [52,53] |
| ITGAL | Hypomethylation | CD4+ T cells | Increased CD11a expression | [40,41] |
| CD40LG | Hypomethylation | CD4+ T cells | B-cell hyperactivation | [36] |
| KIR2DL4 (KIR) | Hypomethylation | CD4+ T cells | Increased KIR expression | [55,56] |
| TNFSF7 | Hypomethylation | CD4+ T cells | Increased CD70 expression | [43-45] |
| 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 | [66,68] |
| 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 | [62,87] |
| 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 | [47,48] |
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.