Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Mortier, Erwan, Woo, Tammy, Advincula, Rommel, Gozalo, Sara, Ma, Averil
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2373851/
https://www.ncbi.nlm.nih.gov/pubmed/18458113
http://dx.doi.org/10.1084/jem.20071913
_version_ 1782154392584060928
author Mortier, Erwan
Woo, Tammy
Advincula, Rommel
Gozalo, Sara
Ma, Averil
author_facet Mortier, Erwan
Woo, Tammy
Advincula, Rommel
Gozalo, Sara
Ma, Averil
author_sort Mortier, Erwan
collection PubMed
description 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.
format Text
id pubmed-2373851
institution National Center for Biotechnology Information
language English
publishDate 2008
publisher The Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-23738512008-11-12 IL-15Rα chaperones IL-15 to stable dendritic cell membrane complexes that activate NK cells via trans presentation Mortier, Erwan Woo, Tammy Advincula, Rommel Gozalo, Sara Ma, Averil J Exp Med Articles 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. The Rockefeller University Press 2008-05-12 /pmc/articles/PMC2373851/ /pubmed/18458113 http://dx.doi.org/10.1084/jem.20071913 Text en © 2008 Mortier et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Articles
Mortier, Erwan
Woo, Tammy
Advincula, Rommel
Gozalo, Sara
Ma, Averil
IL-15Rα chaperones IL-15 to stable dendritic cell membrane complexes that activate NK cells via trans presentation
title IL-15Rα chaperones IL-15 to stable dendritic cell membrane complexes that activate NK cells via trans presentation
title_full IL-15Rα chaperones IL-15 to stable dendritic cell membrane complexes that activate NK cells via trans presentation
title_fullStr IL-15Rα chaperones IL-15 to stable dendritic cell membrane complexes that activate NK cells via trans presentation
title_full_unstemmed IL-15Rα chaperones IL-15 to stable dendritic cell membrane complexes that activate NK cells via trans presentation
title_short IL-15Rα chaperones IL-15 to stable dendritic cell membrane complexes that activate NK cells via trans presentation
title_sort il-15rα chaperones il-15 to stable dendritic cell membrane complexes that activate nk cells via trans presentation
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2373851/
https://www.ncbi.nlm.nih.gov/pubmed/18458113
http://dx.doi.org/10.1084/jem.20071913
work_keys_str_mv AT mortiererwan il15rachaperonesil15tostabledendriticcellmembranecomplexesthatactivatenkcellsviatranspresentation
AT wootammy il15rachaperonesil15tostabledendriticcellmembranecomplexesthatactivatenkcellsviatranspresentation
AT advincularommel il15rachaperonesil15tostabledendriticcellmembranecomplexesthatactivatenkcellsviatranspresentation
AT gozalosara il15rachaperonesil15tostabledendriticcellmembranecomplexesthatactivatenkcellsviatranspresentation
AT maaveril il15rachaperonesil15tostabledendriticcellmembranecomplexesthatactivatenkcellsviatranspresentation