A Chemokine, Interferon (IFN)-(gamma)-Inducible Protein 10 kDa, Is Stimulated by IFN-(tau) and Recruits Immune Cells in the Ovine Endometrium

Proper distribution of immune cells in the uterus is a prerequisite for successful implantation and subsequent placentation, but biochemical signals that govern such events have not been well characterized. In the present study, the cDNA of a chemokine, interferon (IFN)-(gamma)-inducible protein 10 kDa (IP-10), was identified from a cDNA subtraction study between uterine endometrial tissues from Day 17 pregnant and Day 15 cyclic ewes. The effect of IFN-(tau) on IP-10 expression and the involvement of IP-10 in the recruitment of immune cells were then investigated. Northern blot analysis revealed that large amounts of IP-10 mRNA were present during conceptus attachment to maternal endometrium and early placentation. IP-10 mRNA was localized to monocytes distributed in the subepithelial stroma of pregnant but not cyclic uteri. This finding was supported by the discovery of IP-10 mRNA expression in monocytes but not in lymphocytes, uterine epithelial cells, or stromal cells. Moreover, the expression of IP-10 mRNA by the monocytes was stimulated by IFN-(alpha), IFN-(gamma), and IFN-(tau) in a dose-dependent manner, but the expression of IP-10 mRNA by the endometrial explants was most stimulated by IFN-(tau). In a chemotaxis assay, migration of peripheral blood mononuclear cells was stimulated by the addition of IFN-(tau) stimulated-endometrial culture medium, and the effect was significantly reduced by neutralization with an anti-IP-10 antibody. These results suggest that endometrial IP-10 regulated by conceptus IFN-(tau) regulates recruitment and/or distribution of immune cells seen in the early pregnant uterus.