Abstract
Age-related thymic involution is primarily induced by defects in nonhematopoietic thymic epithelial cells (TECs). It is characterized by dysfunction of multiple transcription factors (TFs), such as p63 and FoxN1, and also involves other TEC-associated regulators, such as Aire. These TFs and regulators are controlled by complicated regulatory networks, in which microRNAs (miRNAs) act as a key player. miRNAs can either directly target the 3′-UTRs (untranslated regions) of the TFs to suppress TF expression or target TF inhibitors to reduce or increase TF inhibitor expression and thereby indirectly enhance or inhibit TF expression. Here, we review the current understanding and recent studies about how miRNAs are involved in age-related thymic involution via regulation of TEC-autonomous TFs. We also discuss potential strategies for targeting miRNAs to rejuvenate age-related declined thymic function.
Highlights
The ubiquitous and abundant existence of small noncoding microRNAs in worms, plants, and animals play an important role in the regulation of gene expression, which primarily occurs at posttranscriptional levels via cleavage and/or translational repression of messenger RNAs [1]
Given that many miRNAs are expressed in the thymus with different expression profiles at different developmental stages, we have adequate reasons to infer that miRNAs can be responsible for the regulation of transcription factors (TFs) which are involved in maintaining normal thymic microenvironment that supports T lymphocyte development and controls agerelated thymic involution
We focus on recent research progress which helps to elucidate how miRNA genes regulate thymic epithelial cells (TECs) homeostasis and aging by affecting TEC-specific TFs
Summary
The ubiquitous and abundant existence of small noncoding microRNAs (miRNAs) in worms, plants, and animals play an important role in the regulation of gene expression, which primarily occurs at posttranscriptional levels via cleavage and/or translational repression of messenger RNAs (mRNAs) [1]. Thymocytes possess their own transcription factors (TFs) to control their autonomous activities, many thymic activities during thymic development and aging can be regulated by known TFs in TECs, such as the p63 and FoxN1 [10,11,12,13] Regulation of these TFs remains mysterious and there is limited evidence as to the mechanisms involved. There are two progenitor cell types in the thymus, hematopoietic thymocytes and nonhematopoietic TECs [17] They interact and regulate each other in thymic development, homeostasis, and aging. The mechanism underlying this decline is largely unknown Another very important transcription factor expressed in mTECs is the autoimmune regulator (Aire) gene; the expression of which is declined with age [36, 37]. The specific miRNAs involved in Aire regulation and the mechanisms by which they modulate Aire expression need further investigation
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