Integrin αvβ3 Is Essential for Maintenance of Decidua Tissue Homeostasis and of Natural Killer Cell Immune Tolerance During Pregnancy

Physiological functions of villous trophoblasts are essential for normal implantation and pregnancy, which are under fine regulations. Integrin αvβ3 has been shown to mediate cellular attachment of villous trophoblasts; however, the physiological functions of integrin αvβ3 in pregnancy have not been revealed. Here, we found that suppression of integrin αvβ in vivo by a small molecule inhibitor, SB-273005, resulted in abnormal pregnancy in mice. Mechanistically, suppression of integrin αvβ3 in vivo broke down the tissue homeostasis of the decidua, as revealed by disorganized histology and compromised cellular proliferation in the decidua. Compromised cellular proliferation was also observed in integrin av knocked down human villous trophoblast cell lines, suggesting that compromised proliferation of trophoblast might contribute to the abnormal pregnancy after SB-273005 injection. Moreover, increased NK cells, as well as elevated serum levels of IFN- r in pregnant mice after SB-273005 injection, further linked aggravated pathogenic NK cell responses with the abnormal pregnancy in mice with integrin αvβ3 inhibition. Together, these data demonstrate a role of integrin αvβ3 in maintenance of decidua tissue homeostasis and of NK cell immune tolerance during pregnancy.