A chemokine, interferon (IFN)-γ-inducible protein 10 kDa, is stimulated by IFN-τ and recruits immune cells in the ovine endometrium

Abstract

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)-γ-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-τ 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-α, IFN-γ, and IFN-τ in a dose-dependent manner, but the expression of IP-10 mRNA by the endometrial explants was most stimulated by IFN-τ. In a chemotaxis assay, migration of peripheral blood mononuclear cells was stimulated by the addition of IFN-τ 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-τ regulates recruitment and/or distribution of immune cells seen in the early pregnant uterus.