The Long Noncoding RNA MALAT1 Induces Tolerogenic Dendritic Cells and Regulatory T Cells via miR155/Dendritic Cell-Specific Intercellular Adhesion Molecule-3 Grabbing Nonintegrin/IL10 Axis.

Abstract

By shaping T cell immunity, tolerogenic dendritic cells (tDCs) play critical roles in the induction of immune tolerance after transplantation. However, the role of long noncoding RNAs (lncRNAs) in the function and immune tolerance of dendritic cells (DCs) is largely unknown. Here, we found that the lncRNA MALAT1 is upregulated in the infiltrating cells of tolerized mice with cardiac allografts and activated DCs. Functionally, MALAT1 overexpression favored a switch in DCs toward a tolerant phenotype. Mechanistically, ectopic MALAT1 promoted dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN) expression by functioning as an miR155 sponge, which is essential for the tolerogenic maintenance of DCs and the DC-SIGN-positive subset with more potent tolerogenic ability. The adoptive transfer of MALAT1-overexpressing DCs promoted cardiac allograft survival and protected from the development of experimental autoimmune myocarditis, accompanied with increasing antigen-specific regulatory T cells. Therefore, overexpressed MALAT1 induces tDCs and immune tolerance in heart transplantation and autoimmune disease by the miRNA-155/DC-SIGH/IL10 axis. This study highlights that the lncRNA MALAT1 is a novel tolerance regulator in immunity that has important implications in settings in which tDCs are preferred.

• Authors: Jian Wu, Hanlu Zhang, Yang Zheng, Xiangyuan Jin, Mingyang Liu, Shuang Li, Qi Zhao, Xianglan Liu, Yongshun Wang, Ming Shi, Shengnan Zhang, Jinwei Tian, Yong Sun, Maomao Zhang, Bo Yu
• Journal: Frontiers in immunology (Front Immunol) Vol. 9 Pg. 1847 ( 2018) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 30150986 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cell Adhesion Molecules
• DC-specific ICAM-3 grabbing nonintegrin
• Lectins, C-Type
• MALAT1 long non-coding RNA, human
• MicroRNAs
• Mirn155 microRNA, mouse
• RNA, Long Noncoding
• Receptors, Cell Surface
• Interleukin-10

Topics

• Adoptive Transfer
• Animals
• Autoimmune Diseases (genetics, immunology)
• Cell Adhesion Molecules (metabolism)
• Cell Differentiation
• Cells, Cultured
• Dendritic Cells (immunology)
• Heart Transplantation
• Immune Tolerance
• Interleukin-10 (metabolism)
• Lectins, C-Type (metabolism)
• Lymphocyte Activation
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• MicroRNAs (genetics)
• Models, Animal
• Myocarditis (genetics, immunology)
• Organ Specificity
• RNA, Long Noncoding (genetics)
• Receptors, Cell Surface (metabolism)
• Signal Transduction
• T-Lymphocytes, Regulatory (immunology)