Immune system dysregulation in preeclampsia: a contemporary viewpoint on the role of regulatory T cells and complement activation

Preeclampsia (PE) is a pregnancy complication characterized by arterial hypertension, proteinuria, and multi-organ dysfunction. This review is dedicated to analyzing data on the role of immune system dysregulation in PE pathogenesis, by focusing on two key components: impaired regulatory T cells (Treg) function and hyperactivation of the complement system. Under normal conditions, pregnancy involves the establishment of immune tolerance to the semi-allogeneic fetus, a central element of which is presented by a pool of paternal antigen-specific Tregs. In PE, a Treg quantitative and functional deficiency is observed, leading to an imbalance and a shift towards the proliferation of pro-inflammatory Th17 cells (T-helper 17 cells), which in turn causes systemic inflammation. Concurrently, there is an excessive activation of the complement system, evidenced by elevated anaphylatoxins level (C3a, C5a) and the formation of the membrane attack complex (C5b-9) in the blood and placental tissue. These components damage the trophoblast and endothelium, exacerbating placental dysfunction. A critical insight is the existence of a bidirectional crosstalk between these systems. The activation of anaphylatoxin receptors of complement components C3a and C5a (anaphylatoxin receptors C3a, C5a, C3aR/C5aR) destabilizes Tregs and interferes with their suppressive function, while the Treg deficiency, in turn, weakens the control over complement activation processes, partly due to reduced production of anti-inflammatory cytokines – interleukin-10 (IL-10), transforming growth factor-beta (TGF-β). This self-perpetuating cycle of immune dysregulation underlies the impairment of placentation, systemic endothelial dysfunction, and PE clinical manifestation. Understanding these interconnected mechanisms opens prospects for developing novel targeted strategies aimed at restoring the Treg balance and suppressing pathological complement activity to prevent PE.

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