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.
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.
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长非编码 RNA MALAT1 通过 miR155/树突状细胞特异性细胞间粘附分子 3 抓住非整联蛋白/IL10 轴诱导耐受性树突状细胞和调节性 T 细胞
DOI：
10.3389/fimmu.2018.01847
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发表时间：
2018
影响因子：
7.3
通讯作者：
Yu B
中科院分区：
文献类型：
--
作者：
Wu J;Zhang H;Zheng Y;Jin X;Liu M;Li S;Zhao Q;Liu X;Wang Y;Shi M;Zhang S;Tian J;Sun Y;Zhang M;Yu B
耐受性树突状细胞(TDCs)通过塑造T细胞免疫，在移植后诱导免疫耐受中发挥关键作用。然而，长非编码RNA(LncRNAs)在树突状细胞(DC)的功能和免疫耐受中的作用在很大程度上还不清楚。在这里，我们发现，在接受同种异体心脏移植和活化的DC的耐受小鼠的浸润性细胞中，lncRNA MALAT1上调。在功能上，MALAT1的过表达有利于DC向耐受表型的转变。在机制上，异位MALAT1通过作为miR155海绵促进树突状细胞特异性细胞间黏附分子-3(DC-SIGN)的表达，这对DC的耐受维持和DC-SIGN阳性亚群具有更强的耐受能力是必不可少的。过继转移过表达MALAT1的树突状细胞可促进同种异体心脏移植物存活，防止实验性自身免疫性心肌炎的发生，并伴随抗原特异性调节性T细胞的增加。因此，过表达的MALAT1通过miRNA-155/DC-SIGH/IL10轴诱导心脏移植和自身免疫性疾病的tDCs和免疫耐受。这项研究强调，lncRNA MALAT1是一种新的免疫耐受调节因子，在tDCs首选的环境中具有重要意义。
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.
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CNS 髓磷脂通过与 MOG 的同源相互作用诱导表达 DC-SIGN 的抗原呈递细胞的调节功能。
DOI：
10.1084/jem.20122192
发表时间：
2014-06-30
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
García-Vallejo JJ;Ilarregui JM;Kalay H;Chamorro S;Koning N;Unger WW;Ambrosini M;Montserrat V;Fernandes RJ;Bruijns SC;van Weering JR;Paauw NJ;O'Toole T;van Horssen J;van der Valk P;Nazmi K;Bolscher JG;Bajramovic J;Dijkstra CD;'t Hart BA;van Kooyk Y
通讯作者：
van Kooyk Y
影响因子：
16.8
作者：
Iberg CA;Jones A;Hawiger D
通讯作者：
Hawiger D
影响因子：
15.3
作者：
Geijtenbeek, TBH;van Vliet, SJ;Koppel, EA;Sanchez-Hernandez, M;Vandenbroucke-Grauls, CMJE;Appelmelk, B;van Kooyk, Y
通讯作者：
van Kooyk, Y
影响因子：
7.3
作者：
Flórez-Grau G;Zubizarreta I;Cabezón R;Villoslada P;Benitez-Ribas D
通讯作者：
Benitez-Ribas D
影响因子：
7.3
作者：
Cooles FAH;Anderson AE;Skelton A;Pratt AG;Kurowska-Stolarska MS;McInnes I;Hilkens CMU;Isaacs JD
通讯作者：
Isaacs JD