The filarial nematode product, ES-62 targets IL-22 to mediate protection in collagen-induced arthritis (P5212)
Bibliographic record
Abstract
Abstract Parasitic worms skew immune responses to a Th2-like phenotype, inhibiting Th1/Th17 pathways and expanding regulatory cells such as Tregs. Worms can achieve such immunoregulation by secreting specific products like ES-62, a glycoprotein secreted by the filarial nematode A. viteae. We have previously shown ES-62 to be protective in Collagen-Induced Arthritis, a murine model of rheumatoid arthritis, and that the mechanism associated with protection involves a down-regulation of the cytokine IL-17. We have now analyzed the effects of ES-62 on other Th17-related cytokines focusing on IL-22, a cytokine that has been reported to exhibit both pro and anti-inflammatory actions in animal models of inflammatory disease. In CIA, administration of ES-62 appears to target the IL-17/IL-22 balance in lymph nodes and joints of animals resulting in modulation of the number and inflammatory phenotype of infiltrating and resident cells in the joint, and consequent attenuation of inflammation. Interestingly, using a combination of recombinant IL-22 and blocking antibody in in vivo studies, the precise type of effect of IL-22 on CIA progression was shown to depend largely both on the location of IL-22 action and also the stage at which the cytokine is produced during disease progression. These findings have allowed us to identify a novel mechanism used by the helminth product ES-62 to reduce autoimmune arthritis and they also contribute to our understanding of the complex biology of IL-22
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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) | 0.001 | 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 | 0.001 |
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".