Table 3.

Histone modifications in SLE

Gene	Modification	Cell type studied	Function	Effects in SLE	Ref.
CD8A, CD8B (cluster of differentiation 8A and 8B)	H3K18 deacetylation, H3K27 trimethylation in DN T cells •Epigenetic silencing	CD4+ T cells, CD8+ T cells, DN T cells	Co-receptor to the CD3/T cell receptor complex	Generation of CD3+ CD4− CD8− DN T cells	[14•, 58]
ITGAL (integrin alpha L gene, encoding for CD11A)	Reduced H3K27 trimethylation through histone demethylase JMJD3	CD4+ T cells	Cellular adhesion and costimulation	Increased T cell-mediated inflammation	[100]
IL2 (interleukin-2)	H3K18 deacetylation, H3K27 trimethylation •Epigenetic silencing	CD3+ T cells, CD4+ T cells, effector CD4+ T cells	Proliferation and activation of T cells	Impaired generation of regulatory T cells, reduced activation-induced cell death, and longer survival of autoreactive T cells; impaired function of cytotoxic CD8+ T cells, effector CD4+ T cell differentiation, and cytokine expression	[13, 17, 39, 59]
IL10 (interleukin-10)	H3K18 acetylation •Increased gene expression	CD3+ T cells, CD4+ T cells	Immune regulatory cytokine, inhibition of T cell activation, B cell differentiation, activation, and immunoglobulin production	B cell activation, (auto-) antibody production	[32, 33••, 34, 35]
IL17A (interleukin 17A)	H3K18 acetylation •Increased gene expression	CD3+ T cells, CD4+ T cells, effector CD4+T cells	Induction of chemokines, cytokines, recruitment of neutrophils: defense against bacteria and fungi	Induction of tissue damage in SLE	[19, 37•, 38, 39]
TNF (tumor necrosis factor alpha)	H3 acetylation •Increased gene expression	Monocytes	Monocyte activation, cytokine, and prostaglandin production, priming of mononuclear cells, apoptosis, and oxidative burst, induction of endothelial cell adhesion molecules and cytokine release and T cell apoptosis	Increased monocyte maturation and pro-inflammatory cytokine expression	[101]