Intrinsic NLRP3 inflammasome activity is critical for normal adaptive immunity via regulation of IFN-γ in CD4+ T cells

The NLRP3 inflammasome controls interleukin-1b 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-1b 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.