Peltier, DanielRadosevich, MollyRavikumar, VisweswaranPitchiaya, SethuramasundaramDecoville, ThomasWood, Sherri C.Hou, GuoqingZajac, CynthiaOravecz-Wilson, KatherineSokol, DavidHenig, IsraelWu, JuliaKim, StephanieTaylor, AustinFujiwara, HideakiSun, YapingRao, ArvindChinnaiyan, Arul M.Goldstein, Daniel R.Reddy, Pavan2025-04-072025-04-072021Peltier D, Radosevich M, Ravikumar V, et al. RNA-seq of human T cells after hematopoietic stem cell transplantation identifies Linc00402 as a regulator of T cell alloimmunity. Sci Transl Med. 2021;13(585):eaaz0316. doi:10.1126/scitranslmed.aaz0316https://hdl.handle.net/1805/46849Mechanisms governing allogeneic T cell responses after solid organ and allogeneic hematopoietic stem cell transplantation (HSCT) are incompletely understood. To identify lncRNAs that regulate human donor T cells after clinical HSCT, we performed RNA sequencing on T cells from healthy individuals and donor T cells from three different groups of HSCT recipients that differed in their degree of major histocompatibility complex (MHC) mismatch. We found that lncRNA differential expression was greatest in T cells after MHC-mismatched HSCT relative to T cells after either MHC-matched or autologous HSCT. Differential expression was validated in an independent patient cohort and in mixed lymphocyte reactions using ex vivo healthy human T cells. We identified Linc00402, an uncharacterized lncRNA, among the lncRNAs differentially expressed between the mismatched unrelated and matched unrelated donor T cells. We found that Linc00402 was conserved and exhibited an 88-fold increase in human T cells relative to all other samples in the FANTOM5 database. Linc00402 was also increased in donor T cells from patients who underwent allogeneic cardiac transplantation and in murine T cells. Linc00402 was reduced in patients who subsequently developed acute graft-versus-host disease. Linc00402 enhanced the activity of ERK1 and ERK2, increased FOS nuclear accumulation, and augmented expression of interleukin-2 and Egr-1 after T cell receptor engagement. Functionally, Linc00402 augmented the T cell proliferative response to an allogeneic stimulus but not to a nominal ovalbumin peptide antigen or polyclonal anti-CD3/CD28 stimulus. Thus, our studies identified Linc00402 as a regulator of allogeneic T cell function.en-USPublisher PolicyHematopoietic stem cell tansplantationHistocompatibilityT-lymphocytesArticle