Regulation of IL-5 Receptor on Eosinophil Progenitors in Allergic Inflammation: Role of Retinoic Acid
Bibliographic record
Abstract
We and others have shown that IL-5 plays a central role in eosinophil and basophil differentiation, exerting its effects through the IL-5 receptor (IL-5R). Little is currently known concerning regulation of IL-5Ralpha gene transcription in the context of commitment of hemopoietic progenitor cells to the eosinophil and basophil lineages; recent studies have indicated that IL-5 itself can regulate IL-5Ralpha expression on mature eosinophils. We now provide evidence to indicate that IL-5 can upregulate IL-5Ralpha on bone marrow CD34+ progenitors in vitro, as we have demonstrated in vivo in atopic asthmatics. Given that all-trans retinoic acid (ATRA) is known to modulate some granulopoiesis, causing neutrophilic differentiation, we examined the effects of ATRA on eosinophil/basophil differentiation and IL-5Ralpha expression. In cultures of normal human bone marrow, ATRA selectively suppressed eosinophil/basophil differentiation. Similarly, ATRA inhibited eosinophil/basophil differentiation of cord blood CD34+ cells, while neutrophil differentiation proceeded without impediment. Most importantly, these effects of ATRA on CD34+ cells were associated with selective, dose-dependent inhibition of membrane-bound IL-5Ralpha, upregulation of soluble IL-5Ralpha transcription, but no change in GM-CSF receptor expression. These findings indicate that retinoids can differentially regulate membrane and soluble isoforms of IL-5Ralpha, and that these effects have functional consequences in vitro on eosinophil and basophil differentiation. ATRA may be of therapeutic benefit in allergic inflammatory disorders in which eosinophil differentiation and membrane-bound IL-5R are upregulated.
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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".