| Literature DB >> 27313051 |
Giuseppina Arbore1, Erin E West2, Rosanne Spolski2, Avril A B Robertson3, Andreas Klos4, Claudia Rheinheimer4, Pavel Dutow4, Trent M Woodruff3, Zu Xi Yu5, Luke A O'Neill6, Rebecca C Coll3, Alan Sher7, Warren J Leonard2, Jörg Köhl8,9, Pete Monk10, Matthew A Cooper3, Matthew Arno11, Behdad Afzali1,12, Helen J Lachmann13, Andrew P Cope14, Katrin D Mayer-Barber15, Claudia Kemper1,2.
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.Entities:
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Year: 2016 PMID： 27313051 PMCID： PMC5015487 DOI： 10.1126/science.aad1210
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728