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.
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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 |
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