Unusual timing of CD127 expression by mouse uterine natural killer cells.

ABSTRACT

Decidualization, a progesterone-dependent process that alters endometrial stromal cells at implantation sites in humans and rodents, is accompanied by a highly regulated, NK cell-dominated leukocyte influx into decidual basalis (DB). Whether uNK cells differentiate from uterine progenitor cells is unknown, as are the mechanisms restricting leukocytes to DB. We asked if cells expressing the early NK lineage marker CD127 (IL-7Rα) occurred in mouse decidua. CD127 was absent from gd6.5 decidual lymphoid cells but became expressed by a mature uNK cell subset in gd10.5 DB. DB and transient myometrial structures (MLAp) that ring maternal blood vessels supplying placentae expressed IL-7 and TSLP, the CD127 ligands, but with differing temporal and spatial patterns. UNK cells expressed TSLPR, and study of gd10.5 implantation sites from mice deleted for IL-7, CD127, or TSLPR suggested that IL-7 and its receptor have physiological roles in limiting expansion of immature uNK cells within MLAp, while the TSLP signaling pathway is used in DB to sustain IFN-γ production from a subset of mature uNK cells. Regionalized, dynamic expression of the additional lymphoid organ stromal markers gp38/podoplanin and ER-TR7, but not CD157, were seen by immunohistochemistry in implantation sites, and DB and MLAp contained transcripts for Aire, a tolerance-promoting factor. These observations suggest that CD127(+) NK lineage progenitors are not present in the early postimplantation period of mouse uterus and that decidualized endometrial stroma has key immunoregulatory properties.