Interleukin-11 classic but not trans-signaling is essential for fertility in mice

The cytokine interleukin (IL)-11 activates its target cells through binding to the membrane-bound IL-11 receptor (IL-11R). Female mice deficient in IL-11R (Il11ra−/−) are infertile due to a defect in decidualization when the blastocyst implants. We have recently shown that IL-11 can also signal via a soluble IL-11R (trans-signaling). Which IL-11 pathway is required for fertility in mice is unknown. We confirm that female Il11ra−/−mice, lacking both classic and trans-signaling, are infertile. In contrast, the selective blockade of IL-11 trans-signaling does not affect fertility in mice. These results show that classic, but not trans-signaling of IL-11, is essential for fertility in mice.