Roles of microRNAs in T cell immunity: Implications for strategy development against infectious diseases

Abstract

T cell immunity plays a vital role in pathogen infections.MicroRNA (miRNAs) are small, single-stranded noncoding RNAs that regulate T cell immunity by targeting key transcriptional factors, signaling proteins, and cytokines associated with T cell activation, differentiation, and function. The dysregulation of miRNA expression in T cells may lead to specific immune responses and can provide new therapeutic opportunities against various infectious diseases. Here, we summarize recent studies that focus on the roles of miRNAs in T cell immunity and highlight miRNA functions in prevalent infectious diseases. Additionally, we also provide insights into the functions of extracellular vesicle miRNAs and attempt to delineate the mechanism of miRNA sorting into extracellular vesicles and their immunomodulatory functions. Moreover, methodologies and strategies for miRNA delivery against infectious diseases are summarized. Finally, potential strategies for miRNAbased therapies are proposed.

Quantitative and time-resolved miRNA pattern of early human T cell activation

“…MicroRNAs play a central role in the regulation of T cell functions ( 9 , 10 , 73 ) and the application of miRNAs in immune therapeutics is envisaged ( 15–17 ). We performed time-resolved RNA profiling during the initial 24 h of human CD4+ T cell activation to address imminent challenges in T cell related miRNA research, including the identification of miRNA candidates for future immune manipulation approaches ( 17 , 74 ), the specification of common profiles in miRNA processing ( 75 ) and the characterization of miRNAs in context with T cell functionality.…”

Electroacupuncture Promoted Nerve Repair After Peripheral Nerve Injury by Regulating miR-1b and Its Target Brain-Derived Neurotrophic Factor

“…miRNAs are a class of short (18–25 nucleotides) non-coding small RNAs, which are widely found in eukaryotes. The discovery of miRNAs ranks first among the world’s top 10 technological breakthroughs in Science in 2002. miRNAs are involved in the regulation of various biological processes including autophagy ( Hargarten and Williamson, 2018 ), tumors ( Krump and You, 2018 ), allergic diseases ( Tost, 2018 ), and T-cell immunity ( Giri et al, 2019 ) for mediating gene silencing. Numerous investigations have shown that miRNAs play a vital role in PNI and peripheral nerve repair; for instance, the expression of miRNAs in dorsal root ganglia (DRG) tissues after sciatic nerve injury in rats was significantly changed ( Li et al, 2012 ).…”

Deregulation of SATB2 in carcinogenesis with emphasis on miRNA-mediated control

“…These methods of miR delivery appear highly effective because of the transcriptional machinery that viruses use when involved in infection. However, one major concern is the insertion of virally expressed sequences into the patient's genome, which could cause widespread genomic instability and potential activation and enhancement of oncogenic genes, which could lead to a worse prognosis or the development of secondary cancers or immune deficiency (109). Thus, the development of safe particles that are highly specific toward a cell type or disease is imperative for providing a safe genetic therapeutic effect.…”

“…The most pressing concern is the ability of retrovirus to integrate directly into the host genome. This insertion into the patient genome could provide some detrimental level of mutagenesis and, for example, lead to prolonged oncogene activation (109,111). This, of course, would be contradictory to the therapeutic purpose of the retroviral therapy and is the reason why most current research into viral engineering for therapy has focused on the use of lentiviral vectors (111).…”