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. 2019 Oct 23;10:2520. doi: 10.3389/fimmu.2019.02520

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Copyright © 2019 Winter and Krueger.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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miRNA-mediated control of Treg-cell development. Thymic-derived Treg-cell development begins at the CD4 SP stage of development and proceeds via one of two different pathways. The first Treg precursors to arise are the CD25⁺ population. CD25⁺ precursors require strong TCR signals and IL-2 signaling to mature into CD25⁺Foxp3⁺ Tregs. The alternative pathway of Treg-cell development is characterized by the generation of Foxp3⁺ precursors. Foxp3⁺ precursors develop from comparably weaker TCR signals to CD25⁺ precursors and share little TCR repertoire overlap. As they mature into Tregs they upregulate CD25 and require both IL-4 and IL-15 signaling. Mature Tregs emigrate from the thymus to join the peripheral T cell pool. Total (Dicer/Drosha) and individual miRNAs acting on distinct developmental transitions are indicated. Single positive (SP) and T cell receptor (TCR).