Arbore, G., West, E.E., Spolski, R. et al. (19 more authors) (2016) Intrinsic NLRP3 inflammasome activity is critical for normal adaptive immunity via regulation of IFN-γ in CD4+ T cells. Science, 352 (6292). ISSN 0036-8075
Abstract
The NLRP3 inflammasome controls interleukin-1b maturation in antigen-presenting cells, but
a direct role for NLRP3 in human adaptive immune cells has not been described.We found that
the NLRP3 inflammasome assembles in human CD4+ Tcells and initiates caspase-1–dependent
interleukin-1b secretion, thereby promoting interferon-g production and T helper 1 (TH1)
differentiation in an autocrine fashion. NLRP3 assembly requires intracellular C5 activation and
stimulation of C5a receptor 1 (C5aR1), which is negatively regulated by surface-expressed
C5aR2. Aberrant NLRP3 activity in Tcells affects inflammatory responses in human
autoinflammatory disease and in mouse models of inflammation and infection. Our results
demonstrate that NLRP3 inflammasome activity is not confined to “innate immune cells” but is
an integral component of normal adaptive TH1 responses.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016, American Association for the Advancement of Science. This is an author produced version of a paper subsequently published in Science. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Infection and Immunity (Sheffield) |
Funding Information: | Funder Grant number BRITISH HEART FOUNDATION PG/09/018 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 24 May 2016 15:03 |
Last Modified: | 02 Oct 2018 10:40 |
Published Version: | https://doi.org/10.1126/science.aad1210 |
Status: | Published |
Publisher: | American Association for the Advancement of Science |
Refereed: | Yes |
Identification Number: | 10.1126/science.aad1210 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:99927 |