The Regulatory Activity of Noncoding RNAs in ILCs

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 concur 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 RNA (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.

Transcription factor-driven regulation of ILC1 and ILC3

“…A vastly unexplored and complex area of investigation is that which assesses the potential role of post-transcriptional regulation in ILC1: ILC3 balance. Emerging reports suggest that ILC functionality can be controlled by miRNA, noncoding RNA, or RNA-binding proteins, as reviewed recently [98][99][100][101][102]. However, in terms of TF regulation, insight is limited to the observation that noncoding RNA IncKdm2b can promote the expression of the TF Zfp292, which is required for intestinal ILC3 maintenance, as evidenced by the impaired SI ILC3 cellularity in LncKdm2b -/mice [101].…”

“…A vastly unexplored and complex area of investigation is that which assesses the potential role of post-transcriptional regulation in ILC1:ILC3 balance. Emerging reports suggest that ILC functionality can be controlled by miRNA, noncoding RNA, or RNA-binding proteins, as reviewed recently [ 98. , 99.…”

Heartbreakers or Healers? Innate Lymphoid Cells in Cardiovascular Disease and Obesity

“…Studies which investigate whether and how cILCs are regulated by factors known to control ILC activity in other tissues and disease states are also required. This may include investigation of cILC regulation by neurotransmitters and neuropeptides ( 1 , 84 ), post-transcriptional regulation by non-coding RNAs ( 85 – 87 ), and effects of metabolic dysfunction, such as lactic acidosis ( 88 ) - a known indicator of cardiac stress. Further studies which compare functions and transcriptional profiles of cILCs with more widely studied barrier ILC populations would also be useful.…”

Regulation of mRNA stability contributes to the function of innate lymphoid cells in various diseases

“…In recent years, several studies have revealed that mRNA stability affects the function of ILCs ( 21 , 22 ). The first mechanism of mRNA degradation is exonucleolytic degradation, which removes the poly(A) tail (PAT) by exonucleases, such as the carbon catabolite repression 4 (CCR4)-negative on TATA-less (NOT) complex or poly(A)-specific ribonuclease (PARN).…”