Maternal-fetal immune modulation

Maternal-fetal immune modulation is a complex physiological process by which the maternal immune system recognizes and tolerates the semi-allogeneic fetus while maintaining the ability to defend against pathogens [1, 12]. This process occurs primarily at the maternal-fetal interface, where fetal-derived trophoblasts interact with maternal decidual immune cells, including uterine natural killer (uNK) cells, regulatory T cells (Tregs), and macrophages [3, 14]. Key molecular players include non-classical MHC molecules like HLA-G and HLA-E, which inhibit maternal immune attack, and checkpoint molecules such as PD-L1 and Tim-3 [1, 8]. Dysregulation of this immune balance is a major contributor to pregnancy complications such as recurrent spontaneous abortion, preeclampsia, and preterm birth [7, 11]. Therapeutic strategies aim to restore this tolerance using immunomodulators like progesterone, which promotes a Th2-biased environment, or corticosteroids and IVIG to suppress aberrant immune activation [4, 7]. While not a single molecular target, maternal-fetal immune modulation represents a critical therapeutic area for improving pregnancy outcomes in women with immune-mediated reproductive disorders [11, 12].

Other names

Maternal-fetal immune toleranceFetal-maternal tolerancePregnancy-induced immune toleranceImmunological tolerance in pregnancyMaternal-fetal interface immunity

Modulation of the maternal-fetal interface through the induction of regulatory T cells (Tregs), suppression of natural killer (NK) cell cytotoxicity, and shifting the cytokine profile from Th1 (pro-inflammatory) to Th2 (anti-inflammatory) to prevent fetal rejection [1, 7, 13].