Abstract
Long noncoding RNA (lncRNA) are a class of endogenous, non-protein coding RNAs that are increasingly being associated with various cellular functions and diseases. Yet, despite their ubiquity and abundance, only a minute fraction of these molecules has an assigned function. LncRNAs show tissue-, cell-, and developmental stage-specific expression, and are differentially expressed under physiological or pathological conditions. The role of lncRNAs in the lineage commitment of immune cells and shaping immune responses is becoming evident. Myeloid cells and lymphoid cells are two major classes of immune systems that work in concert to initiate and amplify innate and adaptive immunity in vertebrates. In this review, we provide mechanistic roles of lncRNA through which these noncoding RNAs can directly participate in the differentiation, polarization, and activation of myeloid (monocyte, macrophage, and dendritic cells) and lymphoid cells (T cells, B cells, and NK cells). While our knowledge on the role of lncRNA in immune cell differentiation and function has improved in the past decade, further studies are required to unravel the biological role of lncRNAs and identify novel mechanisms of lncRNA functions in immune cells. Harnessing the regulatory potential of lncRNAs can provide novel diagnostic and therapeutic targets in treating immune cell related diseases.
Highlights
Comprehensive analysis of human transcriptome revealed that our genome is pervasively transcribed [1]
The advances in high throughput sequencing enabled us to carry out transcriptome wide identification of the cellular and tissue expressed long non-coding RNA (lncRNA) repertoire, identifying thousands of novel and differentially expressed lncRNAs in various immune cell types and diseases
The big challenge is to assign a function to these lncRNAs and dissect the molecular mechanism of their action in the context of cellular homeostasis and disease pathogenesis
Summary
Comprehensive analysis of human transcriptome revealed that our genome is pervasively transcribed [1]. Compared to previous estimates of more than 100,000 protein-coding genes encoded by the human genome, genomic and functional analysis only validated 20,000 protein-coding genes [2] This implies that only around 2% of the total human genome sequence is protein coding and the remaining genome transcribes noncoding RNA, govern transcriptional regulation or is transcriptionally inactive. The development, differentiation, and activation of various immune cells has been found to be linked with the expression levels of certain lncRNAs. Numerous differentiation-associated lncRNAs have been identified and a major task is to uncover their functional roles. We will provide an update on the lncRNAs that have been characterized in regulating myeloid and lymphoid cell differentiation, polarization, and the activation of immune response. Induces tolerogenic phenotype in DC and promote Treg polarization by sponging miR-155 and upregulating PU. expression
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