IL-15Rα chaperones IL-15 to stable dendritic cell membrane complexes that activate NK cells via trans presentation - Archive ouverte HAL Access content directly
Journal Articles Journal of Experimental Medicine Year : 2008

IL-15Rα chaperones IL-15 to stable dendritic cell membrane complexes that activate NK cells via trans presentation

(1) , (1) , (1) , (1) , (1)
1
Erwan Mortier
Tammy Woo
  • Function : Author
Averil Ma
  • Function : Author

Abstract

Natural killer (NK) cells are innate immune effectors that mediate rapid responses to viral antigens. Interleukin (IL)-15 and its high affinity IL-15 receptor, IL-15Rα, support NK cell homeostasis in resting animals via a novel trans presentation mechanism. To better understand how IL-15 and IL-15Rα support NK cell activation during immune responses, we have used sensitive assays for detecting native IL-15 and IL-15Rα proteins and developed an assay for detecting complexes of these proteins. We find that IL-15 and IL-15Rα are preassembled in complexes within the endoplasmic reticulum/Golgi of stimulated dendritic cells (DCs) before being released from cells. IL-15Rα is required for IL-15 production by DCs, and IL-15 that emerges onto the cell surface of matured DCs does not bind to neighboring cells expressing IL-15Rα. We also find that soluble IL-15 – IL-15Rα complexes are induced during inflammation, but membrane-bound IL-15 – IL-15Rα complexes, rather than soluble complexes, support NK cell activation in vitro and in vivo. Finally, we provide in vivo evidence that expression of IL-15Rα specifically on DCs is critical for trans presenting IL-15 and activating NK cells. These studies define an unprecedented cytokine – receptor biosynthetic pathway in which IL-15Rα serves as a chaperone for IL-15, after which membrane- bound IL-15Rα – IL-15 complexes activate NK cells via direct cell – cell contact.
Embargoed file
Embargoed file
Ne sera jamais visible
Loading...

Dates and versions

inserm-02442464 , version 1 (16-01-2020)

Identifiers

Cite

Erwan Mortier, Tammy Woo, Rommel Advincula, Sara Gozalo, Averil Ma. IL-15Rα chaperones IL-15 to stable dendritic cell membrane complexes that activate NK cells via trans presentation. Journal of Experimental Medicine, 2008, 205 (5), pp.1213. ⟨10.1084/jem.20071913⟩. ⟨inserm-02442464⟩

Collections

INSERM
13 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More