Autocrine NLPR3 inflammasome activity is critical to normal adaptive immunity via regulation of IFN-γ in CD4+ T cells
Bibliographic record
Abstract
Abstract The NLRP3 inflammasome controls IL-1β maturation in antigen presenting cells but a direct role in human adaptive immune cells has not been described. Here we show that the NLRP3 inflammasome assembles in human CD4+ T cells and initiates caspase-1-dependent IL-1b secretion, thereby promoting IFN-γ production and Th1 differentiation in an autocrine fashion. Importantly, NLRP3 assembly requires intracellular C5 activation and stimulation of C5a receptor 1 (C5aR1), which drive reactive oxygen species (ROS) production. The alternative cell surface expressed C5a receptor 2 (C5aR2) negatively regulates this process. Dysregulation of NLRP3 activity in T cells affects inflammatory responses in autoimmune disease or infection. Firstly, CD4+ T cells from patients with cryopyrin-associated periodic syndromes (CAPS), who have constitutively-active NLRP3, exhibit overactive Th1 responses that are normalized by NLRP3 inhibitor treatment. Secondly, IFN-γ production is impaired in T cells from Nlpr3 −/− or Il1a/Il1b − / − mice upon viral 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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".