Table 1.
lncRNAs with identified immune functions
| LncRNAs in innate immunity | ||||
|---|---|---|---|---|
| lncRNA | Species | Phenotype/function | Proposed mechanism | Reference |
| Lethe | Ms | Pseudogene lncRNA activated by TNFα. Negatively regulates NF-κB. | Binds RelA to inhibit DNA binding | [17] |
| Linc-Cox2 | Ms | Induced in BMDC by LPS (TLR4) and Pam3CSK (TLR2). Regulates inflammatory gene sets. | Interactions with hnRNP-A/B, hnRNP-A2/B1, and SWI/SNF | [32–34] |
| PACER | Hu | Antisense RNA upstrem of COX-2 gene. Promotes COX2 by inducing epigenetic changes at COX2 promoter. | Interacts w/NFkB p50 subunit, prevents it from binding & repressing COX2 | [38] |
| THRIL | Hu | Decreased upon Pam3CSK stimulation and promotes TNFa. Associates with hnRNPL located at TNFa promoter | hnRNPL | [71] |
| AS-IL-1β | Ms | Highly upregulated following LPS stimulation in RAW and peritoneal macrophages. Suppresses IL1b expression. | Regulates RNApolII recruitment to II-1b locus | [72] |
| IL1β-eRNA & IL1 β-RBT46 | Hu | eRNA and site of bidirectional transcription near Il-1b locus. Knockdown attenuates Il-1b and CXCL8 transcription/release. | Unknown | [73] |
| AS-IL-1α | Ms | Induced by Pam3CSK, LPS, polyIC in BMDM to regulate levels of IL-1a | Regulates recruitment of PolII to IL-1a promoter | [74] |
| lnc-DC | Hu | Highly expressed in all DC populations. Promotes CD40, CD80, HLA-DR expression on DCs. | Blocks dephosphorylation of STAT3 | [16] |
| Lnc13 | Hu,Ms | Decreased in inflammation & active celiac. Overlaps 3′ end of Il18rap Levels depend on levels of Dcp2 decapping enzyme. Shown to interact with Hdac1 and hnRNPD. Celiac risk alleles reduce association with hnRNPD | Localized to TSS of targets along with hnRNPD and Hdac1 ; likely a scaffold | [36] |
| lincRNA-EPS | Ms | Downregulated by TLR stimulation. Full deletion results in increased inflammatory genes basally and during inflammation. | Interacts w/hnRNPL through specific RNA motif; loss alters positioning of nucleosomes at target genes | [37] |
| Morrbid | Hu,Ms | Induced by prosurvival cytokines in short-lived myeloid cells (neutrophils, eosinophils, Ly6Chi monocytes). Inhibition results in increased short-lived myeloid cell death. | Interacts with repressive PRC2 complex to target it to Bcl2l11 promoter | [22] |
| lncHSC-1/2 | Ms | Promote HSC function in vitro and in vivo; altered T/B/myeloid reconstitution upon knockdown. | At least partially by promoting recruitment of E2A to target genes | [75] |
| NRAV | Hu | Expressed basally & reduced by infection w/virus. Mouse phenotype is via transgenic overexpression. Negatively regulates ISG expression. | Increases H3K27me3 modifications | [76] |
| iNOS AS | Rat | Antisense RNA in 3′ UTR of iNOS. Promotes expression of iNOS mRNA. | Interactions with 3′ UTR of iNOS mRNA | [77] |
| HOTAIRM1 | Hu | Knockdown results in reduced CD11B and CD18 expression; reduced granulocytic differentiation of cell lines | Activated downstream of RA signaling; mechanism unknown | [39] |
| NKILA | Hu | Induced in response to TNF and IL-1b to regulate NF-kB signaling in breast cancer cell lines. Function in immune cells is unknown. | Blocks IkB phosphorylation | [78] |
| NEAT1 | Hu,Ms | Regulates IL-8 synthesis following immune stimulation | Alters localization of repressor protein SFPQ | [79] |
| lncRHOXF1 | Hu | Suppresses expression of viral response genes in trophoblast progenitors. Viral infection induces lncRHOXF1 expression. | Unknown | [80] |
| lncKdm2b | Ms | Regulates ILC3 homeostasis by promoting ILC3 proliferation | Interacts with Satb1 | [81] |
| Rroid | Ms | Promotes Id2 expression specifically in NK/ILC1 to control their homeostasis | Promotes STAT5 deposition and chromatin accessibility at Id2. RNA-independent | [MOWEL citation] |
| LncRNAs in adaptive immunity | ||||
| NeST / Tmevpg1 | Ms,Hu | Promotes expression of Ifng in Th1 cells downstream of Stat4, Tbet, NFkB, Ets1 | Recruits H3K4 methyltransferases at Ifng promoter | [51–53] |
| NRON | Ms,Hu | Regulates expression of IL-2 in Th1 cells | Maintaints NFAT1 in cytoplasm by providing scaffold for inhibitory NFAT kinases | [44, 46] |
| linc-MAF-4 | Hu | Represses Th2 differentiation by regulating levels of the master Th2 transcription factor c-MAF | Recruits LDS1 and EZH2 to the MAF locus | [47, 48] |
| Rmrp | Ms,Hu | Loss decreases production of IL-17A and IL-17F by Th17 cells. SNP associated with the genetic disease cartilage hair hypoplasia | Required for the interaction of RORγt with DDX5 | [18] |
| Th2-LCR | Ms,Hu | Regulates expression of the IL-4, IL-5, and IL-13 gene cluster in Th2 cells | Associates with WDR5, promotes H3K4 methylation at the II4 and II13 promoters | [54, 55] |
| LincR-Ccr2-5′AS | Ms | Controls a Th2-specific gene expression program including Ccr1, Ccr2, Ccr3, and Ccr5 | Unknown | [49] |
| Fas-AS1 | Ms,Hu | Increases Fas/FasL-mediated apoptosis in B cells, T cells, and other cell types | Binds RBM5, reduces exon skipping in Fas | [82] |
| Gata3-AS | Hu | Coexpressed with GATA3 under Th2-polarizing conditions | Unknown | [49, 83] |
| Flicr | Ms | Partially overlaps FoxP3, specifically expressed in Tregs. Deletion reduces the number of FoxP3lo Tregs and protects against diabetes in NOD mice. Negatively regulated by IL-2 | May alter chromatin structure and accessability at the CNS3/AR5 FoxP3 regulatory region | [57] |