Liver microRNA profile of induced allograft tolerance #MMPMID26950716
Vitalone MJ; Wai L; Fujiki M; Lau AH; Littau E; Esquivel C; Martinez OM; Krams SM
Transplantation 2016[Apr]; 100 (4): 781-90 PMID26950716show ga
Introduction: Although the liver is less immunogenic than other solid organs, most liver transplant recipients receive lifelong immunosuppression. In both experimental models and clinical transplantation, total Lymphoid Irradiation (TLI) has been shown to induce allograft tolerance. Our goal was to identify the microRNAs (miRNAs) expressed in tolerant liver allograft recipients in an experimental model of TLI-induced tolerance. Methods: To identify the miRNAs associated with TLI-induced tolerance we examined syngeneic recipients (Lewis?Lewis) and allogeneic recipients (DA?Lewis) of orthotropic liver transplants that received post-transplant TLI, allogeneic recipients that were not treated post-transplantation and experienced acute rejection, and native DA livers. QPCR miRNA array cards were used to profile liver grafts. Results: We identified 12 miRNAs that were specifically and significantly increased during acute rejection. In early tolerance, 33 miRNAs were altered compared to syngeneic livers, with 80% of the miRNAs increased. In established tolerance 42 miRNAs were altered. In addition, miR-142-5p and miR-181a demonstrated increased expression in tolerant livers (both early and established tolerance) as compared to syngeneic livers. A principal component analysis of all miRNAs assayed, demonstrated a profile in established tolerance that was closely related to that seen in syngeneic livers. Conclusions: The miRNA profile of established tolerant allografts is very similar to syngeneic grafts suggesting tolerance may be a return to an immunological state of quiescence.
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Transplantation 2016 ; 100 (4): 781-90
