4.8 Article

MicroRNAs 24 and 27 Suppress Allergic Inflammation and Target a Network of Regulators of T Helper 2 Cell-Associated Cytokine Production

期刊

IMMUNITY
卷 44, 期 4, 页码 821-832

出版社

CELL PRESS
DOI: 10.1016/j.immuni.2016.01.003

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资金

  1. US National Institutes of Health [HL107202, HL109102, K08AI116949]
  2. Sandler Asthma Basic Research Center
  3. Leukemia & Lymphoma Society
  4. W.M. Keck Foundation
  5. UCSF Diabetes Center (NIH) [P30 DK063720]

向作者/读者索取更多资源

MicroRNAs (miRNAs) are important regulators of cell fate decisions in immune responses. They act by coordinate repression of multiple target genes, a property that we exploited to uncover regulatory networks that govern T helper-2 (Th2) cells. A functional screen of individual miRNAs in primary T cells uncovered multiple miRNAs that inhibited Th2 cell differentiation. Among these were miR-24 and miR-27, miRNAs coexpressed from two genomic clusters, which each functioned independently to limit interleukin-4 (IL-4) production. Mice lacking both clusters in T cells displayed increased Th2 cell responses and tissue pathology in a mouse model of asthma. Gene expression and pathway analyses placed miR-27 upstream of genes known to regulate Th2 cells. They also identified targets not previously associated with Th2 cell biology which regulated IL-4 production in unbiased functional testing. Thus, elucidating the biological function and target repertoire of miR-24 and miR-27 reveals regulators of Th2 cell biology.

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