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.

Hughes and Sawalha Arthritis Research & Therapy 2011 13:245   doi:10.1186/ar3484