Leukemia inhibitory factor protects against graft-versus-host disease while preserving-versus-leukemia

Graft-versus-host disease (GVHD) remains a major complication after allogeneic hematopoietic stem cell transplantation, a widely used therapy for hematologic malig-nancies and blood disorders. Here, we report an unexpected role of cytokine leukemia inhibitory factor (LIF) in protecting against GVHD development. Administrating recom-binant LIF protein (rLIF) protects mice from GVHD-induced tissue damage and lethality without compromising the graft-versus-leukemia activity, which is crucial to prevent tumor relapse. We found that rLIF decreases the infiltration and activation of donor immune cells and protects intestinal stem cells to ameliorate GVHD. Mechanistically, rLIF downregulates IL-12-p40 expression in recipient dendritic cells after irradiation through activating STAT1 signaling, which results in decreased major histocompatibility complex II levels on intestinal epithelial cells and decreased donor T-cell activation and infiltration. This study reveals a previously unidentified protective role of LIF for GVHD-induced tissue pathology and provides a potential effective therapeutic strategy to limit tissue pathology without compromising antileukemic efficacy.

Automated summary

Recombinant LIF protein has been found to protect against tissue damage and mortality caused by GVHD without compromising graft-versus-leukemia activity. This protection is achieved by decreasing the infiltration and activation of immune cells and protecting intestinal stem cells through the activation of STAT1 signaling and downregulation of IL-12-p40 expression.