UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

NLRP3 inflammasome triggers interleukin‐37 release from human monocytes

Gritsenko, Anna; Díaz‐Pino, Rodrigo; López‐Castejón, Gloria; (2022) NLRP3 inflammasome triggers interleukin‐37 release from human monocytes. European Journal of Immunology , 52 (7) pp. 1141-1157. 10.1002/eji.202149724. Green open access

[thumbnail of Eur J Immunol - 2022 - Gritsenko - NLRP3 inflammasome triggers interleukin%E2%80%9037 release from human monocytes.pdf]
Preview
Text
Eur J Immunol - 2022 - Gritsenko - NLRP3 inflammasome triggers interleukin%E2%80%9037 release from human monocytes.pdf - Published Version

Download (7MB) | Preview

Abstract

IL-37 is an anti-inflammatory member of the IL-1 family that dampens inflammation associated with many noncommunicable diseases. However, mechanisms of IL-37 regulation remain understudied. We aimed to investigate the enzymatic cleavage of IL-37 that potentiates extracellular signalling, as well as pathways of IL-37 secretion. In human monocytes, mature IL-37 (mIL-37) was released following canonical NLRP3 inflammasome activation. The release of IL-37 was blocked by inhibiting plasma membrane permeability and in gasdermin-D-deficient THP-1 cells. While the cleavage of IL-37 was found to be constitutive, the release of mIL-37 was blocked in NLRP3-deficient THP-1 cells and by NLRP3 inhibitor MCC950 in THP-1s and primary human monocytes. IL-37 secretion also occurred after 18-h exposure to LPS, independently of the alternative NLRP3 inflammasome. This LPS-dependent IL-37 secretion required plasma membrane permeability, but not conventional protein secretion apparatus. Mutagenesis of the suggested caspase-1 cleavage site (D20) or the proposed alternative cleavage site (V46) did not completely block IL-37 processing. Therefore, we propose a novel pathway in which IL-37 is cleaved by caspase-1-independent mechanisms and released following canonical and alternative NLRP3 inflammasome triggers by differential pathways.

Type: Article
Title: NLRP3 inflammasome triggers interleukin‐37 release from human monocytes
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/eji.202149724
Publisher version: https://doi.org/10.1002/eji.202149724
Language: English
Additional information: © 2022 The Authors. European Journal of Immunology published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: monocytes, NLRP3, caspase-1, gasdermin, interleukin-37
UCL classification: UCL
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 Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/10164740
Downloads since deposit
62Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item