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

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

*Corresponding author for this work
177 Citations (Scopus)


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+ Tcells and initiates caspase-1-dependent interleukin-1β 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.

Original languageEnglish
Article numberaad1210
Issue number6292
Publication statusPublished - 17.06.2016

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)


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