Opposing roles of SWI/SNF chromatin remodeling complex BAF and PBAF in Effector Differentiation during Chronic Viral Infection
Bibliographic record
Abstract
Abstract During chronic viral infection, CD4+ T cells help in the form of IL-21 is critical for the development of highly cytolytic effector CD8+ T cells. However, the exact signaling pathways from IL-21 that regulate CD8+ T cell function remain unclear. The current dogma states that IL-21 predominantly signals through STAT3, to generate effector CD8+ T cells during chronic viral infection. Here, we reveal a novel mechanism of IL-21 signaling via STAT4 for effector CD8+ T cell development following chronic LCMV infection. Furthermore, STAT4-mediated effector differentiation is epigenetically regulated by BAF, a SWI/SNF chromatin remodeling complex. In the absence of either STAT4 or BAF, virus specific CD8+ T cells fail to differentiate into highly cytolytic effector CD8+ T cells capable of controlling viral infection. The effector differentiation phenotype is balanced by PBAF, another component of the SWI/SNF complex, which promotes CD8+ T cell exhaustion during chronic LCMV infection. Conditional knockout of PBAF from CD8+ T cells impairs the development of T cell exhaustion, resulting in immunopathology and mortality of chronic LCMV-infected mice. Interestingly, this phenotype is dependent on the STAT4 and BAF-mediated transcriptional and chromatin changes. Overall, our findings underscore the delicate balance between effector and exhaustion pathways, governed by BAF and PBAF complex, to dictate the outcomes of immunopathology during chronic viral infections.
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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) | 0.000 | 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".