Foxp3 exon 2 regulates keratinocyte-specific IgE and basophil extracellular traps in cutaneous autoimmune photosensitivity
Bibliographic record
Abstract
Abstract Ultraviolet B (UVB) light is a common environmental trigger that can induce flares in several autoimmune diseases, but the mechanisms that mediate UVB-induced photosensitivity remain poorly understood. We used mice which express an autoimmune-driving isoform of Foxp3, called FoxP3ΔE2 mice, to develop a model autoimmune cutaneous photosensitivity. In the steady-state, FoxP3ΔE2 mice have high serum titers of IgE that target skin-associated autoantigens, and increased numbers of IL4-producing T follicular helper cells that target skin-associated proteins (Keratin 14) in the absence of overt immune challenge. After skin exposure to UVB light, FoxP3ΔE2 mice had further elevated IgE, worsened skin inflammation, and increased IgE complex deposition that localized to the challenge site. IgE production in UVB-challenged mice correlated with increased frequencies of germinal center (GC) B cells, elevated percentages of IL-4+ T follicular helper cells, and numbers of basophils with high surface expression of IgE in the draining lymph nodes of UVB-challenged skin. We also observed a significant increase in IgE accumulation, increased numbers of Tug8+ basophil extracellular traps in UVB-challenged skin and increased frequencies of activated plasmacytoid dendritic cells (CD80+CD86+) in the skin and skin-draining lymph nodes of FoxP3ΔE2 mice when compared to wild-type littermates. Collectively, we found that T follicular regulatory cells in FoxP3ΔE2 mice fail to maintain self-tolerance in the GC, resulting in increased production of skin reactive IgE and worsened skin inflammation driven by basophil extracellular trap accumulation in UVB-damaged skin. Supported by grants from the NIH (F32 AI154787, R01 AI136475, R21 AI169418, and R21 AI152444)
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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 | 0.001 | 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 | 0.001 |
| 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".