Long Intergenic Non-Coding RNAs: Novel Drivers of Human Lymphocyte Differentiation

Abstract

Upon recognition of a foreign antigen, CD4+ naïve T lymphocytes proliferate and differentiate into subsets with distinct functions. This process is fundamental for the effective immune system function, as CD4+ T cells orchestrate both the innate and adaptive immune response. Traditionally, this differentiation event has been regarded as the acquisition of an irreversible cell fate so that memory and effector CD4+ T subsets were considered terminally differentiated cells or lineages. Consequently, these lineages are conventionally defined thanks to their prototypical set of cytokines and transcription factors. However, recent findings suggest that CD4+ T lymphocytes possess a remarkable phenotypic plasticity, as they can often re-direct their functional program depending on the milieu they encounter. Therefore, new questions are now compelling such as which are the molecular determinants underlying plasticity and stability and how the balance between these two opposite forces drives the cell fate. As already mentioned, in some cases, the mere expression of cytokines and master regulators could not fully explain lymphocytes plasticity. We should consider other layers of regulation, including epigenetic factors such as the modulation of chromatin state or the transcription of non-coding RNAs, whose high cell-specificity give a hint on their involvement in cell fate determination. In this review, we will focus on the recent advances in understanding CD4+ T lymphocytes subsets specification from an epigenetic point of view. In particular, we will emphasize the emerging importance of non-coding RNAs as key players in these differentiation events. We will also present here new data from our laboratory highlighting the contribution of long non-coding RNAs in driving human CD4+ T lymphocytes differentiation.

Long noncoding RNA #32 contributes to antiviral responses by controlling interferon-stimulated gene expression

“…Some lncRNAs have a critical role in adaptive and innate immunity (31). NeST is one such lncRNA that is well characterized in regard to its role in immunity.…”

Do Memory CD4 T Cells Keep Their Cell-Type Programming: Plasticity versus Fate Commitment?

“…Some signals trigger internal circuits that enforce, reinforce, or destabilize T-cell polarization through multiple mechanisms, including epigenetic modifications (Wang et al 2015). MicroRNAs and long noncoding RNAs (lncRNAs) have also been found to control various aspects of CD4 T-cell differentiation and effector function (Baumjohann and Ansel 2013; Panzeri et al 2015).…”

The emerging role of long non‐coding RNA in spinal cord injury

“…Furthermore, previous studies have identified lncRNAs expressed in B lymphocytes and T lymphocytes development and activation [74,75]. Panzeri et al suggested that long intergenic non-coding RNAs could be novel drivers of human lymphocyte differentiation [76]. Moreover, previous researches performed RNA sequencing of monocytes from four individuals and combined their data with eleven other publicly available datasets and provided a landscape of lncRNAs in monocytes [77].…”