Increased ocular plasma cells induce damaging α-synuclein+ microglia in autoimmune uveitis
Bibliographic record
Abstract
Autoimmune uveitis (AIU) is an immune-inflammatory disease that can lead to blindness. However, incomplete understanding of the involved immune cell subsets and their contributions to retinal injury has hindered the development of effective AIU therapies. Using single-cell RNA sequencing and immunofluorescence, we identified α-synuclein + microglia as the primary subset of damaged ocular cells in the eyes of the experimental autoimmune uveitis (EAU) mouse model. Ocular-infiltrating plasma cells (PCs) were shown to express multiple inflammatory factors, particularly TNF-α, which promoted the production of α-synuclein + microglia. Studies of heterogeneous PC subtypes revealed that MUC1 - PCs represent the primary pathogenic subset, secreting multiple cytokines. Although MUC1 + PCs expressed TGF-β, they exhibited long-lived characteristics and secreted IgG and IgM, thereby prolonging disease progression. Finally, the small G protein Rab1A, also expressed in the PCs of Vogt-Koyanagi-Harada (VKH) patients, was found to mediate autophagy and NF-κB expression, influencing PCs survival and inflammatory responses. Silencing or knocking down Rab1A in PCs inhibited their survival. This study elucidates potential mechanisms underlying the neuroimmune inflammatory response and highlights the previously unrecognized role of infiltrating PCs in AIU, offering novel therapeutic targets for this disease.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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) | 0.001 | 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".