Non-coding RNAs: Key players in T cell exhaustion

Abstract

T cell exhaustion caused by continuous antigen stimulation in chronic viral infections and the tumor microenvironment is a major barrier to successful elimination of viruses and tumor cells. Although immune checkpoint inhibitors should reverse T cell exhaustion, shortcomings, such as off-target effects and single targets, limit their application. Therefore, it is important to identify molecular targets in effector T cells that simultaneously regulate the expression of multiple immune checkpoints. Over the past few years, non-coding RNAs, including microRNAs and long non-coding RNAs, have been shown to participate in the immune response against viral infections and tumors. In this review, we focus on the roles and underlying mechanisms of microRNAs and long non-coding RNAs in the regulation of T cell exhaustion during chronic viral infections and tumorigenesis. We hope that this review will stimulate research to provide more precise and effective immunotherapies against viral infections and tumors.

EPB41L4A-AS1 is required to maintain basal autophagy to modulates Aβ clearance

“…lncRNAs are a class of functional ncRNAs containing more than 200 nucleotides that play significant roles in gene regulation by interacting with transcriptional factors, epigenetic alteration, and sequestration of RNA or protein 26. Growing evidence suggests that lncRNAs participate in various physiological and pathological processes [27][28][29][30][31][32][33][34] , including AD [35][36][37] . Since the identification of EPB41L4A-AS1 as lncRNA, various biological functions have been reported, including regulation of glucose metabolism leading to cancers 13 , T2DM 14 , early recurrent miscarriage 38 , and participating in the expression of a variety of cancer-related genes as competing endogenous RNAs 8,[39][40][41] .…”

EPB41L4A-AS1 modulates Aβ clearance by regulating autophagy-related gene expression

“…lncRNAs are a class of functional ncRNAs containing more than 200 nucleotides that play significant roles in gene regulation by interacting with transcriptional factors, epigenetic alteration, and sequestration of RNA or protein [24]. Growing evidence suggests that lncRNAs participate in various physiological and pathological processes [25][26][27][28][29][30][31][32], including AD [33][34][35]. Since the identification of EPB41L4A-AS1 as lncRNA, various biological functions have been reported, including regulation of glucose metabolism leading to cancers [13], T2DM [14], early recurrent miscarriage [36], and participating in the expression of a variety of cancer-related genes as competing endogenous RNAs [8,[37][38][39].…”

Inference of Developmental Hierarchy and Functional States of Exhausted T Cells from Epigenetic Profiles with Deep Learning

“…Recent studies highlight the unique epigenetic landscape exhibited by exhausted T cells. − Long non-coding RNA (lncRNA) and microRNA (miRNA) have emerged as key players regulating various biological functions, including T-cell activation, development, and differentiation. − DNA methylation, a crucial epigenetic modification, is another essential regulatory factor significantly affecting gene expression in various cellular processes . The availability of comprehensive epigenetic data has opened new avenues for investigating TEX holistically.…”