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...
Autores principales: | , , , , |
---|---|
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 |