Advances in the study of HLA class Ib in maternal-fetal immune tolerance

Abstract

The HLA class Ib molecule is an alloantigen that causes transplant rejection on behalf of individual human and plays an important role in maternal-fetal immune tolerance. Early studies on HLA class Ib focused on the mechanism of HLA-G-induced immune escape, but in recent years, studies on the mechanism of HLA-G have deepened and gradually explored the mechanism of HLA-E and HLA-F, which are also HLA class Ib molecules. In the maternal-fetal interface, trophoblast cells express HLA class Ib molecules to protect the fetus from maternal immune cells by binding to inhibitory receptors of decidual immune cells (DICs) and shifting Th1/Th2 balance toward Th2 bias. Further studies on the molecular mechanism of HLA class Ib molecules provide a reference for its application in the field of clinical assisted reproduction.

Proteome analysis, bioinformatic prediction and experimental evidence revealed immune response down-regulation function for serum-starved human fibroblasts

“…HLA – G is characterized by its tissue restricted pattern of expression and maternal-fetal immune tolerance [ 62 , 63 ]. The immunomodulatory and anti-inflammatory effects of this non-classical HLA class I molecule have repeatedly been reported [ [62] , [63] , [64] ]. Some reports considered the fibroblasts as HLA-G negative cells [ 64 , 65 ].…”

Facing the Challenges in the COVID-19 Pandemic Era: From Standard Treatments to the Umbilical Cord-Derived Mesenchymal Stromal Cells as a New Therapeutic Strategy

“…Immune tolerance and anti-inflammatory properties—UC-MSCs exert immunomodulation properties [ 163 , 175 , 176 ], even related to the expression and release of specific factors, such as the nonclassical HLA class I antigen, HLA-G [ 157 , 177 ], HLA-E, CD276/B7-H3, leukemia inhibitory factor (LIF), indolamine 2,3-dioxygenase-1 (IDO-1), galectin-1 (Gal-1), and heat shock protein 10/Early Pregnancy Factor (HSP10/EPF), being able to modulate or inhibit lymphocyte proliferation [ 175 ]. These factors are involved in tolerogenic processes occurring at the fetal–maternal interface [ 178 , 179 , 180 , 181 , 182 , 183 ], permitting, in turn, the semi-allogeneic embryo to escape surveillance of the maternal immune system. Specifically, HLA-G is an inhibitory molecule involved in immune tolerance and exerts its inhibitory functions interacting with inhibitory receptors Ig-like transcript (ILT) receptors, such as ILT-2, ILT-3, and ILT-4, and killer cell immunoglobulin-like receptor (KIR), two Ig domains, and long cytoplasmic tail 4, KIR2DL4, differentially expressed by NK, T, and antigen-presenting cells [ 184 , 185 ].…”

“…HLA-G also interacts with leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) expressed by CD56 bright CD16 − natural killer (NK) cells that are enriched in the uterus during pregnancy, are poorly cytotoxic, and produce low amounts of IFN-γ as compared with peripheral blood CD56 dim CD16 + NK cells [ 160 ]. HLA-E downregulates the immune response at the fetal–maternal interface, cooperating with classical HLA class I molecules in order to protect target cells from NK-cells-mediated cytotoxicity, interacting with CD94/NKG2A receptor [ 178 ]. CD276/B7-H3 expressed by UC-MSCs is able to inhibit T cell proliferation in a mixed lymphocyte reaction assay [ 175 ], and it is known to promote the survival of Th2 T cells over Th1 ones, together with indirect, noncontact-dependent mechanism mediated by IDO-1 and Gal-1 [ 186 , 187 ].…”

How the Soluble Human Leukocyte Antigen-G levels in Amniotic Fluid and Maternal Serum Correlate with the Feto-Placental Growth in Uncomplicated Pregnancies

“…The ligand-receptor interaction activates angiogenesis and vasculogenesis-related processes and inhibits the cytotoxic activity of NK cells. sHLA-G isoforms induce trophoblast invasion and the remodeling of spiral arteries by producing pro-inflammatory cytokines (IL-6, TNF-alfa) and proangiogenic factors (VEGF-A, MMP) via NK cells [1,6]. sHLA-G promotes the secretion of IL-8 in NK cells and macrophages, which are manifest in trophoblast invasion.…”