Cyclin-dependent kinase 5 activity is required for T cell activation and induction of experimental autoimmune encephalomyelitis
Why this work is in the frame
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Bibliographic record
Abstract
Cyclin-dependent kinase 5 (Cdk5) is a ubiquitously expressed serine/threonine kinase. However, a requirement for Cdk5 has been demonstrated only in postmitotic neurons where there is abundant expression of its activating partners p35 and/or p39. Although hyperactivation of the Cdk5-p35 complex has been found in a variety of inflammatory neurodegenerative disorders, the potential contribution of nonneuronal Cdk5-p35 activity has not been explored in this context. We describe a previously unknown function of the Cdk5-p35 complex in T cells that is required for induction of experimental autoimmune encephalomyelitis (EAE). T cell receptor (TCR) stimulation leads to a rapid induction of Cdk5-p35 expression that is required for T lymphocyte activation. Chimeric mice lacking Cdk5 gene expression in hematopoietic tissues (Cdk5(-/-C)) are resistant to induction of EAE, and adoptive transfer of either Cdk5(-/-C) or p35(-/-) encephalitogenic lymphocytes fails to transfer disease. Moreover, our data reveal a novel mechanism involving Cdk5-mediated phosphorylation of the actin modulator coronin 1a on threonine 418. Cdk5-deficient lymphocytes lack this posttranslational modification of coronin 1a and exhibit defective TCR-induced actin polarization and reduced migration toward CCL-19. These data define a distinct role for Cdk5 in lymphocyte biology and suggest that inhibition of this kinase may be beneficial in the treatment of T cell-mediated inflammatory disorders.
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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 | 0.000 |
| 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) | 0.000 | 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 it