CXCR2-Mediated Granulocytic Myeloid-Derived Suppressor Cells' Functional Characterization and Their Role in Maternal...

To investigate CXC chemokine receptor 2 (CXCR2)-mediated granulocytic myeloid-derived suppressor cells' (MDSCs) (G-MDSCs) functional characterization and their role in maternal-fetal interface. Proportions of CXCR2(+) MDSCs and CXCR2 protein levels in total MDSCs were lower in abortion-prone CBA/J×DBA/2 mice than in CBA/J×BALB/c mice with normal pregnancy. Treatment with CXCR2 neutralizing antibody in vivo at early stage of pregnancy significantly increased the embryo resorption rates and reduced MDSCs abundance in mice from CBA/J×BALB/c matings. Adoptive transfer of MDSCs improved pregnancy outcomes in anti-CXCR2-pretreated CBA/J mice in CBA/J×BALB/C matings. CXCR2 was capable of enhancing the migration of G-MDSCs efficiently instead of monocytic MDSCs (M-MDSCs). In addition to preferential G-MDSC accumulation, arginase I expression as well as arginase I activity of G-MDSCs were regulated by CXCR2. CXCL1, as one of CXCR2 ligands, correlated well with CXCR2-mediated G-MDSCs migration and arginase I activity. CXCR2/CXCL1 axis promotes G-MDSC recruitment and facilitates arginase I expression and activity of these cells at maternal-fetal interface. These findings provide comprehensive insights into how G-MDSCs are recruited to decidual tissues and how local G-MDSCs maintain pregnancy tolerance.