Analysis of the Contributions of l-Selectin and CXCR3 in Mediating Leukocyte Homing to Pregnant Mouse Uterus
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PROBLEM: Dynamic changes occur in endometrial immune cell populations during pregnancy but regulatory events promoting cell recruitment to the uterus are not established. Ovarian steroid hormones promote l-selectin and alpha4-integrin-mediated interactions between human peripheral natural killer (NK) cells and uterine endothelium while CXCR3, CXCR4 and their ligands are implicated in homing of human uNK cells to decidua. METHOD OF STUDY: Mice genetically-ablated for l-selectin or CXCR3 were studied. Morphometric analyses of implantation sites and assays of cell function (in vitro adhesion; in vivo homing following adoptive cell transfer) were undertaken. RESULTS: Leukocytes home to anti-mesometrial decidua with l-selectin making an early (<6 hr in vivo) contribution. Unexpectedly, CXCR3 deletion had no effect on homing but reduced the ability of uNK cells to modify placental spiral arterioles. CONCLUSIONS: Redundant mechanisms underlie homing of leukocytes to the uterus and their importance can be evaluated by an in vivo approach described herein.
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