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

2016; American Association for the Advancement of Science; Volume: 352; Issue: 6292 Linguagem: Inglês

10.1126/science.aad1210

1095-9203

Giuseppina Arbore, Erin E. West, Rosanne Spolski, Avril A. B. Robertson, Andreas Klos, Claudia Rheinheimer, Pavel Dutow, Trent M. Woodruff, Zu Xi Yu, Luke O'neill, Rebecca C. Coll, Alan Sher, Warren J. Leonard, Jörg Köhl, Peter N. Monk, Matthew A. Cooper, Matthew Arno, Behdad Afzali, Helen J. Lachmann, Andrew P. Cope, Katrin D. Mayer-Barber, Claudia Kemper,

Kawasaki Disease and Coronary Complications

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.