S1P1 regulation of pulmonary tertiary lymphoid tissues
Bibliographic record
Abstract
Abstract Pulmonary tertiary lymphoid tissues (TLT) emerge as central regulators of antigen-specific responses in the lung and they have been associated with the severity of chronic respiratory diseases such as hypersensitivity pneumonitis (HP). The sphingosine-1-phosphate receptor S1P1 is a potent modulator of lymphoid organ biology and of the TH17 response, which is often associated with HP and TLT formation in the lung. We recently identified a novel immunogenic agent commonly found in the bioaerosols of working environments that induces an HP-like disease and potently stimulates TLT formation in the lung. We first aimed to determine if the ability of this agent to induce TLTs was related to their propensity to trigger a TH17 response in the lung. Secondly, we determined whether or not S1P1 acts as a modulator of pulmonary TLTs. Mice were exposed intra-nasally to Methanosphaera stadtmanae (MSS) for a 3-weeks time period in order to induce TLT formation. Upon MSS rechallenge, Il-17 expression was increased by 3 fold in the lung supporting the involvement of this cytokine in the current model. Among five homeostatic chemokines/proinflammatory cytokines tested, we found that CXCL13 was the most significantly increased by the MSS rechallenge (4.9-fold), supporting its involvement in TLT formation in response to MSS. S1P1 pharmacological agonism led to a 50% inhibition of Il-17 and Cxcl13 expression in the lung, which translated into a full inhibition of TLT expansion in response to the MSS rechallenge; and into a 77% alleviation of the pulmonary neutrophilic response. This study unravels a role for the S1P pathway in the regulation of TLTs as well as its interplay with the TH17 response in the lung.
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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) | 0.002 | 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".