MicroRNA Regulation of T-Lymphocyte Immunity: Modulation of Molecular Networks Responsible for T-Cell Activation, Differentiation, and Development

Abstract

MicroRNAs (miRNA) are a class of small non-coding RNAs that constitute an essential and evolutionarily conserved mechanism for post-transcriptional gene regulation. Multiple miRNAs have been described to play key roles in T lymphocyte development, differentiation and function. In this review we highlight the current literature regarding the differential expression of miRNAs in various models of mouse and human T cell biology and emphasize mechanistic understandings of miRNA regulation of thymocyte development, T cell activation, and differentiation into effector and memory subsets. We describe the participation of miRNAs in complex regulatory circuits shaping T cell proteomes in a context-dependent manner. It is striking that some miRNAs regulate multiple processes, while others only appear in limited functional contexts. It is also evident that the expression and function of specific miRNAs can differ between mouse and human systems. Ultimately, it is not always correct to simplify the complex events of T cell biology into a model driven by only one or two master regulator miRNAs. In reality, T cell activation and differentiation involves the expression of multiple miRNAs with many mRNA targets and thus, the true extent of miRNA regulation of T cell biology is likely far more vast than currently appreciated.

Recent trends in microRNA research into breast cancer with particular focus on the associations between microRNAs and intrinsic subtypes

“…The first randomized controlled trial indicated that a relationship exists between increased numbers of TILs and pCR rates. 111 Podshivalova et al 112 suggested that miRNA have an important role in T-lymphocyte activation and also described a mechanism for regulating the impact of miRNA. Jasinski-Bergner reported that natural killer cell and CD8-positive T-lymphocyte ligands are both regulated by the number of miRNAs.…”

Longitudinal Examination of the Intestinal Lamina Propria Cellular Compartment of Simian Immunodeficiency Virus-Infected Rhesus Macaques Provides Broader and Deeper Insights into the Link between Aberrant MicroRNA Expression and Persistent Immune Activation

“…Numerous studies have shown that microRNAs (miRNAs), a class of small noncoding RNAs, can posttranscriptionally regulate immune cell proliferation/differentiation/migration, cytokine signaling/production, and the inflammatory response (6)(7)(8). miRNA dysregulation has been associated with several chronic inflammatory diseases, such as inflammatory bowel disease (9), experimental autoimmune encephalomyelitis (10), multiple sclerosis (11), and rheumatoid arthritis (12).…”

Immunological and classical subtypes of oral premalignant lesions

“…Of note, 14/46 miRNAs overexpressed in the immunological subtype, have been involved in the activation or differentiation of lymphocytes and/or monocytes. 30,31 Using the miRNet tool, we identified 3,251 validated mRNAs targets of the 31/61 differentially expressed miRNAs (Figure 3). Interestingly, 970/3,251 (30%) mRNAs targets were also found to be differentially expressed between the two classes of OPL (Wilcoxon test, Q-value< 0.05).…”

“…This result was consistent with the overexpression of 14 miRNAs in the immunological subtype that have been involved in the activation or differentiation of lymphocytes and/or monocytes. 30,31 In particular, miR-142-5p expression was higher in the immunological subtype compared to the classical subtype while its decreased expression was associated with a higher risk of oral cancer development in the immunological subtype only. A study of microRNA profiles during progression of oral leukoplakia to cancer has shown the complex deregulation of miR-142-5p expression during oral carcinogenesis.…”