Science · 2016 · 511 citations · 45 references
Life SciencesCell BiologyImmunologyAdaptive ImmunityInflammationInnate ImmunityAdaptive Immune ResponsesInflammasome ActivationInflammatory SignalingInnate Immune ActivationNod-like ReceptorsT Cell ActivationAntigen Presenting CellsAntigen-presenting Cell MaturationAutoinflammatory MechanismsInflammatory T Cell ResponsesInterferon Gamma ProductionInterferon ProductionNlr Family Pyrin Domain-containing 3 InflammasomeNlrp3 Inflammasome
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. NLRP3 assembly requires intracellular C5 activation and stimulation of C5a receptor 1 (C5aR1), which is negatively regulated by surface‑expressed C5aR2. We found that the NLRP3 inflammasome assembles in human CD4⁺ T cells, initiates caspase‑1‑dependent IL‑1β secretion, and promotes IFN‑γ production and Th1 differentiation in an autocrine manner; aberrant NLRP3 activity in T cells alters inflammatory responses in human autoinflammatory disease and in mouse models of inflammation and infection; and our results show that NLRP3 inflammasome activity is not confined to innate immune cells but is an integral component of normal adaptive Th1 responses.
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.
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