Characterizing the role of Blimp-1 in regulating encephalitogenic T cells in CNS autoimmunity (IRC8P.483)
Bibliographic record
Abstract
Abstract Effector and recall responses of T cells play an important role in the pathogenesis of Multiple Sclerosis and EAE. B lymphocyte induced maturation protein-1 (Blimp-1) is a transcription factor that plays important roles in regulating immunity. However, its role in regulating encephalitogenic T cells in EAE has not been characterized. Using YFP/Blimp-1 reporter mice, we analyzed Blimp-1 expression in myelin-specific CD4 T cells in vitro and in vivo. Blimp-1 expression correlates with the encephalitogenicity of myelin-specific CD4 T cells, which is highly expressed in encephalitogenic Th1 and Th17 cells, but not in non-encephalitogenic Th17 cells. Moreover, Blimp-1 is highly expressed in myelin-specific CD4 T cells in the draining lymph nodes, spleen and CNS during EAE development, specifically in activated CD44+IL7Rα+CD4 T cells. As IL-23 significantly enhances the encephalitogenicity of myelin-specific CD4 T cells, we determined if IL-23 upregulates Blimp-1 expression. Our data showed that exogenous IL-23 significantly enhances Blimp-1 expression in myelin-specific CD4 T cells and Blimp-1 is highly expressed in IFNγ+, IL-17+ and IFNγ+ and IL-17 double positive cells in draining LN cells, splenocytes and CNS infiltrating cells. In addition, we determined the role of Blimp-1 in regulating T cell migration and EAE development. Together, our findings suggest that Blimp-1 might play an important role in regulating autoreactive T cells and the development of CNS autoimmunity.
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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 | 0.002 | 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 | 0.001 |
| 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".