GRANZYME-D, GRANZYME-E, GRANZYME-F, AND GRANZYME-G ARE REGULATED THROUGH PREGNANCY AND BY IL-2 AND IL-15 IN GRANULATED METRIAL GLAND-CELLS

Granulated metrial gland (GMG) cells are NK cells that proliferate and differentiate within the murine uterus during pregnancy. They have be en predicted to play important roles in nurturing the embryo, normal p lacentation, and uterine tissue remodeling. GMG cell differentiation i s manifested by the accumulation of the cytolytic mediators, perforin, granzyme A, and granzyme B, within cytoplasmic granules. The signalin g mechanisms required for GMG cell differentiation are largely unknown , although recent in vitro assays have implicated IL-15 in these event s. In this report, we demonstrate that granzymes D, E, F, and G (granz ymes D-G) are also expressed in GMG cells but at a later stage in preg nancy when compared with granzyme A expression. Whereas granzyme A is expressed in early to mid-gestation, the expression of granzymes D-G p eak in mid- to late gestation. In addition, we show that the expressio n patterns of IL-2R beta and the IL-2R gamma mRNAs overlap with that o f granzyme D-G mRNAs in the pregnant uterus, Finally, we demonstrate t hat granzymes D-G are up-regulated by IL-2 and IL-15 in primary cultur es containing GMG cells. Taken together, these results suggest that IL -2 and/or IL-15 may regulate GMG cell differentiation in vivo, and tha t granzymes D-G may have different functions than granzyme A during pr egnancy.