Project Grant R01AI201522

The National Institute of Allergy and Infectious Diseases awarded The Leland Stanford Junior University $782,736 on September 1, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to support research on the induction of acquired fetal tolerance through an erythropoietin-dependent pathway.

The research investigates how T-cell-mediated tolerance is initiated and maintained during human pregnancy, drawing on work examining erythropoietin receptor signaling in conventional type 1 dendritic cells in solid organ transplantation. The hypothesis posits that placental erythropoietin production and trophoblast apoptosis, driven by tissue hypoxia at the maternal-fetal interface, converge to drive fetal antigen-specific regulatory T-cell induction and CD8 T-cell exhaustion through a dendritic cell-dependent mechanism. The research employs primary human tissue, transgenic mouse models, and next-generation spatial biology assays to elucidate these mechanisms. Work includes analysis of dendritic cells, regulatory T-cells, and CD8 T-cells in decidual tissue and uterine draining lymph nodes from healthy pregnancies and women with recurrent pregnancy loss; comparative analysis of human tissue composition and structure against transgenic mouse experimental results; and culture experiments using human dendritic cells and decidual explants with trophoblasts to determine whether the placental secretome alone is sufficient to induce tolerogenic dendritic cell phenotypes.

Performance occurs in Palo Alto, California, with a period of performance extending through August 31, 2031.