Activation of neonatal mouse lung ILC2s by endogenous IL-33 impacts type 2 responses later in life
Bibliographic record
Abstract
Abstract Neonatal lung immunity is functionally distinct from adults as responses to environmental antigens are predominantly type 2 biased, and early exposure has been linked to the development of airway allergic diseases. Recently our lab and others have shown that endogenous release of IL-33 due to the stresses of the first few breaths of life leads to expansion and activation of group 2 innate lymphoid cells (ILC2s) from 10 days (D10) to two weeks after birth. However, the amount of IL-33 is lower than in allergen-treated lungs of adult mice, and neonatal lungs do not show signs of type 2 inflammation. Nevertheless, our analyses of IL-33KO and ILC2 deficient pups have suggested that the activation of neonatal lung ILC2s by endogenous IL-33 drives type 2 immunity. As well, neonatal ILC2s labeled with BrdU persist in adulthood. Therefore, we further characterized neonatal lung ILC2s and investigated the effects of neonatal activation on ILC2 functions later in life. Our microarray analysis of neonatal ILC2s showed more similarity to IL-33 activated than naïve adult ILC2s. D10 ILC2s have a high expression of IL-25R, similar to activated adult ILC2s, and can be stimulated by IL-25. We compared IL-33KO and WT ILC2s in adult mice and there was no difference in the phenotype or number of lung ILC2s. However, intranasal (IN) IL-33 injections induced significantly fewer IL-5+IL-13+ ILC2s in IL-33KO mice. We then injected IL-33 into IL-33KO neonates to test the effect on adult ILC2s. Preliminary results show that IN IL-33 into neonatal IL-33KO mice rescue the impaired response of adult IL-33KO ILC2s. These results suggest that the weak activation by the endogenous IL-33 of neonatal lung ILC2s has significant effects on the development of type 2 responses later in life.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| 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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".