Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall 4EF
Background: Tolerogenic dendritic cells(DCs) by shaping T cells immunity and inducing Tregs play critical roles in the induction of allograft tolerance in transplantation. Long noncoding RNAs (lncRNAs) have emerged as important regulators of the immune system. However, the role of lncRNAs in DC function and transplant immunity is largely unknown.
Methods: The lncRNA MALAT1 was identified in tolerized murine cardiac allografts(treated with anti-CD40L mAb) compared with rejecting cardiac allografts by microarray and qRT-PCR. The contribution of MALAT1 on the functional phenotype of DCs in vitro and cardiac allograft immunity was further performed.
Results: LncRNA MALAT1 was upregulated in the infiltrating cells of tolerized mice cardiac allografts and activated DCs. Functionally, MALAT1 overexpression favored a switch of the DC to a tolerant phenotype. The adoptive transfer of MALAT1-overexpressing DCs into recipient mice promoted cardiac allograft survival and induced antigen-specific regulatory T cells. Mechanistically, by functioning as a miR155 sponge, ectopic MALAT1 promoted DC-SIGN expression, which is essential for the tolerogenic maintance of DCs and DC-SIGN positive subset with more potent tolerogenic ability. Meanwhile IL10 is required for DC-SIGN-mediated DC tolerogenic functions following MALAT1 overexpression.Additionally, MALAT1 directly interacted with NF-κB p65 in nuleus forming a negative regulatory loop to control inflammatory cytokines transcription.
Conclusions: The ectopic MALAT1 in DCs induced tolerogenic function switch, Tregs expansion and prolonged allograft survival via miR155/DC-SIGN/IL10 axis. This study highlights the lncRNA MALAT1 as a novel tolerance regulator in immunity, with important implications in transplantation.
CITATION INFORMATION: Zhang M., Wu J., Zhang H., Liu M., Zheng Y., Jin X., Li S., Zhao Q., Liu X., Sun Y., Yu B. The LncRNA MALAT1 Induces Tolerogenic DCs and Antigen Specific Tregs Subsequently Mediating Cardiac Allograft Tolerance in Mice via MiR-155/DC-SIGN/IL10 Axis Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Zhang M, Wu J, Zhang H, Liu M, Zheng Y, Jin X, Li S, Zhao Q, Liu X, Sun Y, Yu B. The LncRNA MALAT1 Induces Tolerogenic DCs and Antigen Specific Tregs Subsequently Mediating Cardiac Allograft Tolerance in Mice via MiR-155/DC-SIGN/IL10 Axis [abstract]. https://atcmeetingabstracts.com/abstract/the-lncrna-malat1-induces-tolerogenic-dcs-and-antigen-specific-tregs-subsequently-mediating-cardiac-allograft-tolerance-in-mice-via-mir-155-dc-sign-il10-axis/. Accessed March 8, 2021.
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