The cooling compound icilin attenuates autoimmune neuroinflammation through modulation of the T‐cell response
Bibliographic record
Abstract
The synthetic supercooling drug, icilin, and its primary receptor target, the cation channel transient receptor potential (TRP) melastatin‐8 (TRPM8), have been described as potent negative regulators of inflammation in the colon. The aim of this study was to determine whether the anti‐inflammatory action of icilin could potentially be used to treat autoimmune neuroinflammatory disorders, such as multiple sclerosis (MS). During experimental autoimmune encephalomyelitis (EAE)—a CD4 + T cell‐driven murine model of MS—we found that both wild‐type (WT) and TRPM8‐deficient EAE mice were protected from disease progression during icilin treatment, as evidenced by delays in clinical onset and reductions in neuroinflammation. In vitro , icilin potently inhibited the proliferation of murine and human CD4 + T cells, with the peripheral expansion of autoantigen‐restricted T cells similarly diminished by the administration of icilin in mice. Attenuation of both TRPM8 –/– and TRP ankyrin‐1 –/– T‐cell proliferation by icilin was consistent with the WT phenotype, which suggests a mechanism that is independent of these channels. In addition, icilin treatment altered the expressional profile of activated CD4 + T cells to one that was indicative of restricted effector function and limited neuroinflammatory potential. These findings identify a potent antiinflammatory role for icilin in lymphocyte‐mediated neuroinflammation and highlight clear pleiotropic effects of the compound beyond classic TRP channel activation.—Ewanchuk, B. W., Allan, E. R. O., Warren, A. L., Ramachandran, R., Yates, R. M. The cooling compound icilin attenuates autoimmune neuroinflammation through modulation of the T‐cell response. FASEB J. 32,1236‐1249 (2018). www.fasebj.org
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.004 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".