LIF

Leukemia inhibitory factor (LIF) is a cytokine in the interleukin-6 (IL-6) family. It is encoded by the LIF gene in humans and many vertebrates and is secreted by a variety of cell types, including fibroblasts and placental cells. LIF functions by binding to a receptor complex consisting of the LIF receptor (LIFR) and the signal-transducing subunit gp130, which activates intracellular signaling pathways such as JAK/STAT3, MAPK, and PI3K/Akt.

In development and stem cell biology, LIF has a prominent role. In mice, LIF is essential for maintaining the self-renewal of embryonic stem cells through STAT3 signaling, and LIF knockout female mice are infertile due to impaired embryo implantation. In humans and other primates, LIF can support neural cell survival and differentiation, but human embryonic stem cells rely more on fibroblast growth factor 2 (FGF2) and Activin/Nodal signaling for pluripotency than on LIF alone.

Expression and regulation of LIF reflect its pleiotropy. It is produced by multiple cell types, including bone marrow stromal cells, macrophages, and placental cells, and its expression is influenced by cytokines and hormonal signals. The name derives from its observed ability to inhibit the proliferation of certain leukemia cells in vitro.

Clinical and research context: LIF is widely used in basic science to study cytokine signaling and to sustain mouse embryonic stem cells in culture. It has been investigated for potential therapeutic roles in neuroprotection and tissue repair, but clinical applications remain experimental and highly context-dependent, with possible proinflammatory effects in some settings.