Li, LKim, H TNellore, APatsoukis, NPetkova, VMcDonough, SPolitikos, INikiforow, SSoiffer, RAntin, J HBallen, KCutler, CRitz, JBoussiotis, V A2014-03-112014Li, L., H. T. Kim, A. Nellore, N. Patsoukis, V. Petkova, S. McDonough, I. Politikos, et al. 2014. “Prostaglandin E2 promotes survival of naive UCB T cells via the Wnt/β-catenin pathway and alters immune reconstitution after UCBT.” Blood Cancer Journal 4 (1): e178. doi:10.1038/bcj.2013.75. http://dx.doi.org/10.1038/bcj.2013.75.2044-5385http://nrs.harvard.edu/urn-3:HUL.InstRepos:11879933The outcome of umbilical cord blood transplantation (UCBT) is compromised by low hematopoietic stem cell (HSC) doses leading to prolonged time to engraftment, delayed immunological reconstitution and late memory T-cell skewing. Exposure of UCB to dimethyl-prostaglandin E2 (dmPGE2) increases HSC in vivo. We determined that exposure of UCB T lymphocytes to dmPGE2 modified Wnt signaling resulting in T cell factor (TCF)-mediated transcription. Wnt signaling upregulated interleukin (IL)-7R and IL-2Rβ, resulting in enhanced survival mediated by the homeostatic cytokines IL-7 and IL-15. dmPGE2 also induced components of the Wnt pathway and Wnt receptors, thereby priming UCB T cells to receive signals via Wnt ligands in vivo. We observed that the Wnt transcription factor TCF7 and its target EOMES were elevated in the T cells of patients who received PGE2-treated UCBs. Consistent with the role of Wnt/β-catenin signaling to induce and maintain naive, memory precursors and long-lived central memory CD8+ cells, these patients also had increased fractions of CD8+CD45RO-CD62L+ plus CD8+CD45RO+CD62L+ subsets encompassing these T-cell populations. These effects of the PGE2/Wnt/β-catenin axis may have significant implications for harnessing immunity in the context of UCBT, where impaired immune reconstitution is associated with late memory T-cell skewing.en-USumbilical cord blood transplantationimmune reconstitutionprostaglandin E2Wnt/β-catenin pathwayJournal Article2014-03-1110.1038/bcj.2013.75