Table 3.

The effects of sex hormones on cells of immune system.

Sex Hormone	DNA Methylation Changes	Target Gene	Biological Effect	References
17-β-estradiol—high concentration	A crucial element in the passive and active DNA demethylation activities both on the DNA and histones.	T helper cell	Amplifies Th2 responses: raises IL-4, IL-10, TGF-β, promotes IRF-1, inhibits TNFα and IL-17.	[122,123,124]
		Treg cell	Promotes differentiation and activity: stimulates FoxP3 and PD-1.	[125,126]
		Nk cell	Declines activity: raises IL-10, TGF-β.	[123,127]
		B cell	Amplifies survival of autoreactive B cells: reduces BCR, increases CD22.	[122]
		Macrophages	Decreases activity: decreases IL-6, IL-1β and TNFα, raises IL-10.	[123,128]
		Dendritic cells	Reduces activity: reduces IL-6, IL-1β and TNFα.	[122,123]
Progesterone	DNA methylation status is still not yet confirmed.	T helper cell	Promotes Th2 response: increases IL-4, IL-10, TGF-β and decreases IFNγ and IL-12. Reduces Th1 and Th17 responses: decreases IFNγ, IL-12, and IL-17.	[122,129,130]
		NK cells	Reduces activity: reduces INFγ.	[122,130]
		B cell	Decreases class-switch recombination and T cells.	[122,129,130]
		Macrophages	Lowers activity: reduces nitric oxide production, TNFα, and FcγR.	[130]
		Dendritic cells	Decreases activity: decreases TLR-mediated IFNα production.	[131]
PSG1a	Highly expressed in myoblasts and strongly downregulated after differentiation.		Enhances IL-10 and TGF-β production.	[132,133]