IL-1β Induces Human Endothelial Surface Expression of IL-15 by Relieving let-7c-3p Suppression of Protein Translation.

Autor:	Mullan CW; Department of Immunobiology, Yale School of Medicine, New Haven, CT.; Department of Surgery, Yale School of Medicine, New Haven, CT., Summer L; Department of Immunobiology, Yale School of Medicine, New Haven, CT., Lopez-Giraldez F; Department of Genetics, Yale School of Medicine, New Haven, CT.; Yale Center for Genome Analysis, Yale School of Medicine, West Haven, CT., Tobiasova Z; Department of Immunobiology, Yale School of Medicine, New Haven, CT., Manes TD; Department of Immunobiology, Yale School of Medicine, New Haven, CT., Yasothan S; Department of Immunobiology, Yale School of Medicine, New Haven, CT., Song G; Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT.; Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China., Jane-Wit D; Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT.; Department of Cardiology, VA Connecticut Healthcare System, West Haven, CT., Saltzman WM; Department of Biomedical Engineering, Yale University, New Haven, CT.; Department of Chemical & Environmental Engineering, Yale University, New Haven, CT.; Department of Cellular & Molecular Physiology, Yale University, New Haven, CT.; Department of Dermatology, Yale University, New Haven, CT., Pober JS; Department of Immunobiology, Yale School of Medicine, New Haven, CT.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2024 Nov 01; Vol. 213 (9), pp. 1338-1348.
DOI:	10.4049/jimmunol.2400331
Abstrakt:	Expression of IL-15 on the surface of human graft endothelial cells (ECs) bound to the IL-15Rα subunit can increase the activation of CTLs, potentiating allograft rejection. Our previous work showed that surface expression of this protein complex could be induced by alloantibody-mediated complement activation through increased IL-1β synthesis, secretion, and autocrine/paracrine IL-1-mediated activation of NF-κB. In this article, we report that cultured human ECs express eight differently spliced IL-15 transcripts. Remarkably, IL-1β does not alter the expression level of any IL-15 transcript but induces surface expression independently of RNA polymerase II-mediated transcription while requiring new protein translation. Mechanistically, IL-1β causes an NF-κB-mediated reduction in the level of microRNA Let-7c-3p, thereby relieving a block of translation of IL-15 surface protein. Let7c-3p anti-miR can induce EC surface expression of IL-15/IL-15Rα in the absence of complement activation or of IL-1, enabling IL-15 transpresentation to boost CD8 T cell activation. Because of the complexity we have uncovered in IL-15 regulation, we recommend caution in interpreting increased total IL-15 mRNA or protein levels as a surrogate for transpresentation. (Copyright © 2024 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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