The Emerging Functions of Long Noncoding RNA in Immune Cells: Autoimmune Diseases

Figure 2

The functions of lncRNAs in autoimmune cells, T cells, B cells, macrophages, NK, and dendritic cells. (a) Lnc-DC expression is needed for differentiation of human monocytes into dendritic cells. Lnc-DC promotes STAT3 phosphorylation through inhibiting the action of Src homology region 2 domain-containing phosphatase-1 (SHP-1) [18]. (b) LincRNA-COX-2 is located in COX2 gene in mouse bone marrow-derived macrophages. It has extensive effects on inflammatory gene expression, repressing the transcription of anti-inflammatory genes in nonstimulated cells and promoting the expression of proinflammatory genes following Pam3Csk4 exposure via an interaction with hnRNP-A/B and A2/B1 [13]. (c) LincR-Ccr2-5′AS positively regulates the expression of genes involved in immunity particularly; lincR-Ccr2-5′AS regulates the transcription of several chemokine receptor genes in mouse, CD4+ TH2 cells, STAT-6 pathway [17]; (d) LincRNA (THRIL), as a key player in regulating the TNF-α and its expression was obviously lower during the acute phase of immune response. It was identified as an antisense lncRNA through a RNA-protein complex with hnRNPL and promotes TNF transcription [24]. (e) PACER is located upstream of the Cox2 transcriptional start site and is expressed in the antisense direction for innate immune response helping in gene expression, production of inflammatory mediators, and finally differentiation of monocytes/macrophages and dendritic cells [25]. (f) Chromatin modifier, for example, NeST, a lincRNA located downstream of Ifng which promotes the transcription of Ifng, WDR5, core submits of the MLL H3K4 methyltransferases, and facilitate the histone methylation at the Ifng locus, which promotes the transcription of Ifng in Th1 CD4+/CD8+ T cells. lncRNA also typically interacts with other transcripts and regulates miRNAs pathway, translation splicing, and RNA turnover [15]. LncRNAs characterized to regulate the abundance of genomically neighbouring (cis- and trans-acting) gene products [37].