Soluble interleukin-15 complexes are generated in vivo by type I interferon dependent and independent pathways

PloS One
Scott M AnthonyKimberly S Schluns

Abstract

Interleukin (IL)-15 associates with IL-15Rα on the cell surface where it can be cleaved into soluble cytokine/receptor complexes that have the potential to stimulate CD8 T cells and NK cells. Unfortunately, little is known about the in vivo production of soluble IL-15Rα/IL-15 complexes (sIL-15 complexes), particularly regarding the circumstances that induce them and the mechanisms responsible. The main objective of this study was to elucidate the signals leading to the generation of sIL-15 complexes. In this study, we show that sIL-15 complexes are increased in the serum of mice in response to Interferon (IFN)-α. In bone marrow derived dendritic cells (BMDC), IFN-α increased the activity of ADAM17, a metalloproteinase implicated in cleaving IL-15 complexes from the cell surface. Moreover, knocking out ADAM17 in BMDCs prevented the ability of IFN-α to induce sIL-15 complexes demonstrating ADAM17 as a critical protease mediating cleavage of IL-15 complexes in response to type I IFNs. Type I IFN signaling was required for generating sIL-15 complexes as in vivo induction of sIL-15 complexes by Poly I:C stimulation or total body irradiation (TBI) was impaired in IFNAR-/- mice. Interestingly, serum sIL-15 complexes were also induced ...Continue Reading

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Citations

Feb 26, 2016·Nature Reviews. Cancer·Belinda S ParkerPaul J Hertzog
Jul 9, 2020·Immunotherapy·Mohadeseh Haji AbdolvahabLeila Farahmand
Dec 28, 2018·Proceedings of the National Academy of Sciences of the United States of America·Rosa M Santana CarreroKimberly S Schluns
May 18, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Scott M AnthonyKimberly S Schluns
Aug 18, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ryan T SowellAmanda L Marzo
Nov 19, 2020·Journal for Immunotherapy of Cancer·Piera Filomena FioreBruno Azzarone
Apr 6, 2021·Frontiers in Immunology·Xiang Wang, Xiang-Yu Zhao
Aug 22, 2017·Immunology Letters·Tanya O Robinson, Kimberly S Schluns
Aug 11, 2021·The Journal of Clinical Investigation·Tanya O RobinsonKimberly S Schluns

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Methods Mentioned

BETA
ELISAs
ELISA
flow cytometry

Software Mentioned

GraphPad
Excel
GraphPad Prism
Flowjo

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