TSLP directly impairs pulmonary Treg function: association with aberrant tolerogenic immunity in asthmatic airway
Bibliographic record
Abstract
BACKGROUND: Even though thymic stromal lymphopoietin (TSLP) has been implicated in the development of allergic inflammation, its influence on immune tolerance mediated by regulatory T cells (Treg) have not been explored. We aimed to dissect the influence of TSLP on immunosuppressive activities of Treg and its potential consequences in human allergic asthma. METHODS: In vitro culture system was utilized to study the effects of TSLP on human Treg. The functional competency of pulmonary Treg from a cohort of 15 allergic asthmatic, 15 healthy control, and 15 non-allergic asthmatic subjects was also evaluated by suppression assays and flow cytometric analysis. RESULTS: Activated pulmonary Treg expressed TSLP-R and responded to TSLP-mediated activation of STAT5. TSLP directly and selectively impaired IL-10 production of Treg and inhibited their suppressive activity. In human allergic asthma, pulmonary Treg exhibited a significant decrease in suppressive activity and IL-10 production compared to healthy control and non-allergic asthmatic counterparts. These functional alterations were associated with elevated TSLP expression in bronchoalveolar lavage fluid (BAL) of allergic asthmatic subjects. Furthermore, allergic asthmatic BAL could suppress IL-10 production by healthy control pulmonary Treg in a TSLP-dependent manner. CONCLUSIONS: These results provide the first evidences for a direct role of TSLP in the regulation of suppressive activities of Treg. TSLP mediated inhibition of Treg function might present a novel pathologic mechanism to dampen tolerogenic immune responses in inflamed asthmatic airway.
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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 | 0.000 |
| 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".