Purpose: Tolerogenic dendritic cells have been gaining interest as an efficient means of promoting antigen-specific tolerance in organ transplantation. Long noncoding RNA NEAT1 plays an important role in the innate immune response. However, the role of NEAT1 in the immunogenic function of DCs and allograft immunity remains poorly understood.

Methods and Results: A microarray was performed to analyze the different expression of lncRNAs in cardiac allografts of mice and NEAT1 was identified down-regulated in tolerized cardiac allografts. In vitro, NEAT1 was increased in LPS stimulated bone marrow-derived CD11c⁺ DCs by qRT-PCR. Bioinformatic databases and CHIP assay confirmed that transcriptional factor E2F1-induced H3K27ac could active the expression of NEAT1. Functionally, knockdown of NEAT1 was found to induce a tolerogenic phenotype on CD11c⁺ DCs, characterized by downregulation of CD80, CD86 and MHCII, a reduced costimulatory potential as well as production of the immunomodulatory IL-10. Regulatory T cells were significantly increased in siNEAT1-DCs, however, the proliferation of T cells was suppressed. Finally, BALB/c recipients transfused with siNEAT1-DCs had significantly prolonged allograft survival and cardiac allografts showed slight cell infiltration. The regulatory T cells were increased in recipients spleen transfused with siNEAT1-DCs.

Conclusion: NEAT1 can induce tolerogenic DCs and prolonged cardiac allograft survial and was transcriptionally activated by E2F1-mediated EH3K27ac. These findings suggest a new, indirect effector mechanism by which NEAT-inducing antigen-presenting cells contribute to immune tolerance. Furthermore, NEAT1-inducing DCs may be a promising approach for immunotherapy in the heart transplantation.

CITATION INFORMATION: Wu J., Zheng Y., Li S., Zhang M., Zhang H., Zheng X., Sun Y., Yu B. Long Noncoding RNA NEAT1 Induces Tolerogenic Dendritic Cells in Heart Transplantation Am J Transplant. 2017;17 (suppl 3).

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