The Regulatory Activity of Noncoding RNAs in ILCs.

Alessio Grimaldi,Helena Stabile,Giuseppe Sciumè,Giuseppe Pietropaolo,Angela Gismondi,Andrea Kosta,Cristina Capuano,Angela Santoni,Cinzia Fionda

doi:10.3390/cells10102742

Alessio Grimaldi, Helena Stabile + Show 7 more

Open Access

https://doi.org/10.3390/cells10102742

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Abstract

Innate lymphoid cells (ILCs) are innate lymphocytes playing essential functions in protection against microbial infections and participate in both homeostatic and pathological contexts, including tissue remodeling, cancer, and inflammatory disorders. A number of lineage-defining transcription factors concurs to establish transcriptional networks which determine the identity and the activity of the distinct ILC subsets. However, the contribution of other regulatory molecules in controlling ILC development and function is also recently emerging. In this regard, noncoding RNAs (ncRNAs) represent key elements of the complex regulatory network of ILC biology and host protection. ncRNAs mostly lack protein-coding potential, but they are endowed with a relevant regulatory activity in immune and nonimmune cells because of their ability to control chromatin structure, RNA stability, and/or protein synthesis. Herein, we summarize recent studies describing how distinct types of ncRNAs, mainly microRNAs, long ncRNAs, and circular RNAs, act in the context of ILC biology. In particular, we comment on how ncRNAs can exert key effects in ILCs by controlling gene expression in a cell- or state-specific manner and how this tunes distinct functional outputs in ILCs.

Highlights

Innate lymphoid cells (ILCs) are a heterogeneous population of innate lymphocytes, which originate from the common lymphoid progenitor but lack antigen-specific receptors [1]
It is clear that noncoding RNAs (ncRNAs) can control the gene expression by generating finetuned regulatory circuits
Tight control mechanisms guarantee the concerted action of multiple ncRNAs generating complex regulatory RNA networks strictly interconnected with many other regulatory elements

Summary

Introduction

Innate lymphoid cells (ILCs) are a heterogeneous population of innate lymphocytes, which originate from the common lymphoid progenitor but lack antigen-specific receptors [1]. These findings suggest that the overlapping miRNA repertoires could be used by innate and adaptive lymphocytes to generate similar effector functions; we cannot exclude that this occurs for ILC1 vs Th1 and ILC3 vs Th17 In this regard, several miRNAs described in Th cells could be able to target shared pathways in ILCs. For instance, miR-29 has been shown to be essential for suppression of Th1 differentiation and for limiting NK cell functions by directly targeting the LDTFs T-bet and Eomes and the type 1 signature cytokine, IFN-γ [64,65]. The miR-125a-5p, let-7e-5p, and miR-574-3p resulted as highly expressed in dILC3 These miRNAs can potentially regulate genes involved in different biological processes (e.g., innate immune response, cytokine production, and tissue remodeling), sharing target genes implicated in the regulation of inflammatory response (e.g., IL6, IL6R, and STAT3), and angiogenesis (e.g., angiopoietin 2). These transcription products play a crucial role in the fine-tuning of nuclear organization, RNA processing, transcriptional and post-transcriptional machinery and in the modulation of crucial functions of other ncRNAs [78]

LncRNAs and ILCs

Findings

Conclusions