Systemic lupus erythematosus, regulatory T cells and pregnancy

Abstract

Systemic lupus erythematosus (SLE) is the most common autoimmune disease affecting women of reproductive age and is associated with poor maternal and fetal outcomes. CD4(+)CD25(+) Treg cells are a subset of T lymphocytes with potent immunosuppressive activity that play crucial roles in controlling immunological self tolerance. Evidence suggests that they are augmented in pregnancy, especially in the first trimester, suggesting an important role in early placental development. The literature describing Treg cells in SLE is conflicting, but SLE is associated with reduced numbers and functionally defective Treg cells, which may predispose pregnant women with the disease to pregnancy complications. This article discusses the role of Treg cells in SLE and pregnancy, and how these cells may contribute to poor pregnancy outcome in SLE-affected women.

Sex affects immunity

“…The important suppressive role of Tregs during pregnancy are highlighted in females with SLE. Females affected by SLE have low numbers of and/or dysfunctional Tregs, associated with difficulties in becoming pregnant and maintaining pregnancy [70] Treg functional deficits have been implicated in RA and MS [71,72].…”

Seminal Fluid and the Generation of Regulatory T Cells for Embryo Implantation

“…However, in view of the effect of prior pregnancy on Treg cells, it is important in such comparisons to take into account the confounding effect of parity. Additionally, there is evidence that chronic disease states impacting systemic immune function can alter reduce Treg cells, including in asthma, allergy, autoimmune disease, and HIV infection . Baboon studies suggest that Treg cells might contribute to the effects of endometriosis on fertility, because after induction of endometriosis lesions both peripheral blood and endometrial Treg cells were reduced …”

Reproductive Environment in Patients with SLE

“…Besides Th1 and Th2 cells, there is a third subset of CD4+ T-helper cells called Th17 cells, which, like Treg cells, are implicated in pregnancy and maternal immune tolerance to the fetus [14]. These Th17 cells are defined by their ability to produce IL-17, a pro-inflammatory cytokine that promotes development of Th17 cells and interestingly, in the presence of a tolerance milieu, drives differentiation to Treg cells [21]. Both Treg and Th17 cells require transforming growth factor beta (TGF-β) for differentiation, but the copresence of IL-6 favors differentiation of pathogenic Th17 cells as it can inhibit the generation of FoxP3+ in Treg cells induced by TGF-β [22].…”