[Research Articles] RNA-seq of human T cells after hematopoietic stem cell transplantation identifies Linc00402 as a regulator of T cell alloimmunity
Mechanisms 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 pr...
Source: Science Translational Medicine - Category: Biomedical Science Authors: Peltier, D., Radosevich, M., Ravikumar, V., Pitchiaya, S., Decoville, T., Wood, S. C., Hou, G., Zajac, C., Oravecz-Wilson, K., Sokol, D., Henig, I., Wu, J., Kim, S., Taylor, A., Fujiwara, H., Sun, Y., Rao, A., Chinnaiyan, A. M., Goldstein, D. R., Reddy, P Tags: Research Articles Source Type: research
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