Chandran, P. Anoop and Keller, Andreas and Weinmann, Lasse and Seida, Ahmed Adel and Braun, Matthias and Andreev, Katerina and Fischer, Birgitt and Horn, Evi and Schwinn, Stefanie and Junker, Markus and Houben, Roland and Dombrowski, Yvonne and Dietl, Johannes and Finotto, Susetta and Woelfl, Matthias and Meister, Gunter and Wischhusen, Joerg (2014) The TGF-beta-inducible miR-23a cluster attenuates IFN-gamma levels and antigen-specific cytotoxicity in human CD8(+) T cells. JOURNAL OF LEUKOCYTE BIOLOGY, 96 (4). pp. 633-645. ISSN 0741-5400, 1938-3673
Full text not available from this repository. (Request a copy)Abstract
Cytokine secretion and degranulation represent key components of CD8(+) T-cell cytotoxicity. While transcriptional blockade of IFN- and inhibition of degranulation by TGF- are well established, we wondered whether TGF- could also induce immune-regulatory miRNAs in human CD8(+) T cells. We used miRNA microarrays and high-throughput sequencing in combination with qRT-PCR and found that TGF- promotes expression of the miR-23a cluster in human CD8(+) T cells. Likewise, TGF- up-regulated expression of the cluster in CD8(+) T cells from wild-type mice, but not in cells from mice with tissue-specific expression of a dominant-negative TGF- type II receptor. Reporter gene assays including site mutations confirmed that miR-23a specifically targets the 3UTR of CD107a/LAMP1 mRNA, whereas the further miRNAs expressed in this clusternamely, miR-27a and -24target the 3UTR of IFN- mRNA. Upon modulation of the miR-23a cluster by the respective miRNA antagomirs and mimics, we observed significant changes in IFN- expression, but only slight effects on CD107a/LAMP1 expression. Still, overexpression of the cluster attenuated the cytotoxic activity of antigen-specific CD8(+) T cells. These functional data thus reveal that the miR-23a cluster not only is induced by TGF-, but also exerts a suppressive effect on CD8(+) T-cell effector functions, even in the absence of TGF- signaling.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | UP-REGULATION; GROWTH; EXPRESSION; TARGETS; MICRORNAS; APOPTOSIS; PROTEIN; IDENTIFICATION; INVASIVENESS; DEGRADATION; antigen-specific T cells; miRNA induction; tolerance; tumor targets |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I > Prof. Dr. Gunter Meister |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 Aug 2019 11:16 |
| Last Modified: | 13 Aug 2019 11:16 |
| URI: | https://pred.uni-regensburg.de/id/eprint/9509 |
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