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Paper Reading 01 MicroRNA-17 Modulates Regulatory T Cell Function by Targeting Co-regulators of the Foxp3 Transcription Factor  Huang-Yu Yang, Joseph Barbi, Chao-Yi Wu,… Huabin Li, and Fan Pan et al. Immunity (2016) We know the Treg cell transcription factor Foxp3 works in concert with other co-regulatory molecules, including Eos. To determine the transcriptional signature and characteristic suppressive phenotype of Treg cells. In this paper, the authors report that the inflammatory cytokine interleukin-6 (IL-6) actively repressed Eos expression through microRNA-17 (miR-17). This targeting of the Eos transcript and that of other Foxp3 co-regulators, including Satb1 and IRF-4, resulted in decreased Treg cell suppressive function and the acquisition of Teff cell characteristics, including the production of effector cytokines. Based on previous study that the miR-17-92 miRNA cluster has been implicated in immune regulation and lymphomagenesis. The inflammatory cytokine IL-6 induces miR-17-92 expression, and ectopic expression of the miR-17-92 cluster in T cells causes autoimmunity in mice. This paper firstly verified that T-cell-specific deletion of miR-17-92 enhances Treg cell function T-cell-specific through using miR-17-92-null (mir17-92-/-) mice by breedingmir17-92flox/flox mutants to CD4-Cre+ transgenic mice. In addition, they identified Eos as a potential target ofmiR-17-92 by screening a panel of miR-17-92 miRNAs for the ability to bind the30 UTR of the Eos, Irf4, Gata1, Lef1, and Satb1 transcripts bioinformatically. Then they utilized a luciferase reporter assay to demonstrate that IL-6 augments miR-17 expression through HIF-1. In vitro, they also demonstrate that miR-17 can destabilize the suppressive functions and gene expression of established and differentiating Treg cells. What is more, in vivo, they certified that miR-17 modulates the suppressive activity of Treg cells. All in all, their studies show miR-17 provides a potent layer of Treg cell control through targeting Eos and additional Foxp3 co-regulators. http://dx./10.1016/j.immuni.2016.06.02 02 Metabolic coordination of T cell quiescence and activation  Nicole M. Chapman,Mark R. Boothby and Hongbo Chi Nature Reviews Immunology Naive T cells are actively maintained in a quiescent state, which is defined as being in the G0 stage of the cell cycle and having low metabolic, transcriptional and translational activities. In this paper, the authors show that immune cues and nutrients permit and modulate metabolic programs and signaling networks to communicate in a two-way manner to facilitate resting exits. Understanding the process of modulating T cell quiescence will be key to developing new ways to regulate protective and pathological T cell responses in human disease. Naive T cells are actively maintained in a quiescent state, which is defined as being in the G0 phase of the cell cycle and has low metabolic, transcriptional and translational activities. This quiescent state is different from the peripheral tolerance imposed by regulatory T cells (Treg cells) or the non-reactivity due to inappropriate TCR stimulation or co-stimulation. Naive T cells are ready to activate, driving their clonal expansion and effector functions. This activation is mediated by a process called quiescent withdrawal, which occurs after antigen stimulation and co-stimulation and before the first cell division. T cells develop in the thymus and mature into naive T cells before entering the circulation, which is maintained by the binding of the auto peptide-MHC molecule and the cytokine IL-7 to the T cell receptor (TCR). At the time of antigen stimulation, naive T cells differentiate into effector T cells and longevity memory T cells (TM cells). If the naive T cell pool changes, adverse reactions to pathogens, tumors and vaccines, or development of immunodeficiency or autoimmunity may occur. Therefore, it is important founders and how naive T cells balance and activate. All in all, this review summarizes the metabolic regulation of resting and resting withdrawal of naive T cells, as well as a small degree of resting TM cells. The authors first described the metabolic characteristics of resting and resting exits; then they discussed how to actively maintain T cell quiescence through intracellular signaling and metabolic programs, and were forced by Treg cell-derived mechanisms; next, they detailed how the metabolic program Drivingantigen-dependent activation of naive T cells, and how nutrients and other microenvironmental factors regulate the balance between T cell quiescence and activation; finally, they summarized how these metabolic programs interact with immune signals, discussing the regulation of T cell quiescence future direction and therapeutic significance. https://www./articles/s41577-019-0203-y-cles41577-019-0203- END |
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