IL-18 is required for the TH1-adaptation of TREG cells and the selective suppression of TH17 responses in acute and chronic infections
Bibliographic record
Abstract
Interleukin (IL)-18, a member of the IL-1 family of alarmins, is abundantly released in the lungs following influenza A (IAV) infections yet its role in orchestrating the local adaptive immune response remains ill defined.Through genetic disruption of the IL-18 receptor, we demonstrate that IL-18 not only promotes pulmonary T H 1 responses but also influences regulatory T cells (T REG ) function in the infected lungs.As the response unfolds, T REG cells accumulating in the lungs express Helios, T-bet, CXCR3, and IL-18R1 and produce interferon γ in the presence of IL-12.During IAV, IL-18R1 is required for T REG cells to control T H 17, but not T H 1, responses and promote a return to lung homeostasis, revealing a novel mechanism of selective suppression.Moreover, this observation was not limited to the lungs, as skin-localized T REG cells require an IL-18 signal to specifically suppress IL-17A production by T H 17 and γδ T cells in a model of chronic cutaneous Leishmania major infection.Overall, these results uncover how IL-18 orchestrates the tissue adaptation of T REG cells to selectively favor T H 1 over T H 17 responses during T H 1-driven immune responses and provide a novel perspective into how IL-18 dictates the immune response during viral and parasitic infections.
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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 | 0.001 |
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".