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

T helper 1 immunity requires complement-driven NLRP3 inflammasome activity in CD4+ T cells

Arbore, G; West, EE; Spolski, R; Robertson, AA; Klos, A; Rheinheimer, C; Dutow, P; ... Kemper, C; + view all (2016) T helper 1 immunity requires complement-driven NLRP3 inflammasome activity in CD4+ T cells. Science , 352 (6292) , Article aad1210. 10.1126/science.aad1210. Green open access

[thumbnail of aad1210_CombinedPDF_v3.pdf]
Preview
Text
aad1210_CombinedPDF_v3.pdf - Accepted Version

Download (5MB) | Preview

Abstract

The NLRP3 inflammasome controls interleukin-1β 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(+) T cells and initiates caspase-1-dependent interleukin-1β secretion, thereby promoting interferon-γ production and T helper 1 (T(H)1) 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 T cells 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 T(H)1 responses.

Type: Article
Title: T helper 1 immunity requires complement-driven NLRP3 inflammasome activity in CD4+ T cells
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1126/science.aad1210
Publisher version: http://dx.doi.org/10.1126/science.aad1210
Language: English
Additional information: Copyright © 2016 American Association for the Advancement of Science. This is the author's version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science vol. 352 no. 6292, doi: 10.1126/science.aad1210
Keywords: Adaptive Immunity, Animals, Antigens, CD46, Autocrine Communication, CD4-Positive T-Lymphocytes, Carrier Proteins, Complement Activation, Complement C5a, Cryopyrin-Associated Periodic Syndromes, Disease Models, Animal, HEK293 Cells, Humans, Immunity, Innate, Inflammasomes, Inflammation, Interferon-gamma, Mice, Mice, Mutant Strains, Reactive Oxygen Species, Receptor, Anaphylatoxin C5a, Receptors, Antigen, T-Cell, Receptors, Chemokine, Th1 Cells
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 Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: https://discovery.ucl.ac.uk/id/eprint/1505945
Downloads since deposit
246Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item