UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

Complement receptor CD46 co-stimulates optimal human CD8(+) T cell effector function via fatty acid metabolism

Arbore, G; West, EE; Rahman, J; Le Friec, G; Niyonzima, N; Pirooznia, M; Tunc, I; ... Kemper, C; + view all (2018) Complement receptor CD46 co-stimulates optimal human CD8(+) T cell effector function via fatty acid metabolism. Nature Communications , 9 , Article 4186. 10.1038/s41467-018-06706-z. Green open access

[img]
Preview
Text
Arbore_s41467-018-06706-z.pdf - ["content_typename_Published version" not defined]

Download (2MB) | Preview

Abstract

The induction of human CD4+ Th1 cells requires autocrine stimulation of the complement receptor CD46 in direct crosstalk with a CD4+ T cell-intrinsic NLRP3 inflammasome. However, it is unclear whether human cytotoxic CD8+ T cell (CTL) responses also rely on an intrinsic complement-inflammasome axis. Here we show, using CTLs from patients with CD46 deficiency or with constitutively-active NLRP3, that CD46 delivers co-stimulatory signals for optimal CTL activity by augmenting nutrient-influx and fatty acid synthesis. Surprisingly, although CTLs express NLRP3, a canonical NLRP3 inflammasome is not required for normal human CTL activity, as CTLs from patients with hyperactive NLRP3 activity function normally. These findings establish autocrine complement and CD46 activity as integral components of normal human CTL biology, and, since CD46 is only present in humans, emphasize the divergent roles of innate immune sensors between mice and men.

Type: Article
Title: Complement receptor CD46 co-stimulates optimal human CD8(+) T cell effector function via fatty acid metabolism
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41467-018-06706-z
Publisher version: http://doi.org/10.1038/s41467-018-06706-z
Language: English
Additional information: Copyright © The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: http://discovery.ucl.ac.uk/id/eprint/10060941
Downloads since deposit
5Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item