CX3CR1 Expression Is Required for the Development of Pain like Behavior in a Mouse Model of Autoimmune Peripheral Neuropathy
Bibliographic record
Abstract
Introduction/Aim: Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy are prototypic autoimmune peripheral neuropathy (APN) which represent a serious neurological emergency. Although current treatment options have proven effective, many patients still present with a severe disease course, pain and residual deficits. We have reported that B7.2 transgenic L31 mice spontaneously develop inflammatory peripheral neuropathy. We also showed that an injury to peripheral nerve in L31 mice facilitates the development of APN. Both effector/memory CD8 T cells and B7.2+ macrophages are required for disease initiation. Here, we highlighted the importance of CX3CR1 expression in disease pathogenesis and in the development of pain like behavior in L31 mice. Methods: L31 mice were crossed with CX3CR1KO mice, and the effect on macrophage phagocytic ability, activated CD8 T cells function and pathology were assessed. Results: CX3CR1 expression was strongly upregulated in sciatic nerve of symptomatic L31 mice which correlated with increased phagocytic ability. Enhanced phagocytosis in L31 mice was impeded in L31/CX3CR1−/- mice. Also, injury failed to trigger APN in L31 mice deficient of CX3CR1 expression. APN associated sensory deficits positively correlated with the amount of CX3CR1 expression. In addition, CX3CR1 deficiency led to a high number of dying monocytes, macrophages and activated CD8 T cells suggesting that CX3CR1 signaling may be crucial for their survival. Lastly, sciatic nerve histology showed no myelin and axon damage in L31/CX3CR1−/- mice. Discussion/Conclusions: These data suggest that CX3CR1 expression are critical for the development of APN in L31 mice. CX3CR1 expressing macrophages contribute to disease pathogenesis via enhanced antigen phagocytosis and presentation.
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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 | 0.000 |
| 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".