The Transcription Factor ELF4 Restrains the Inflammatory Potential of CD4+ T Cells
Bibliographic record
Abstract
Abstract ELF4 is a member of the ETS family of transcription factors, known to be involved in the regulation and development of immune cells. Yet, the primary function of ELF4 was unknown prior to our discovery of patients with loss-of-function mutations in ELF4 that cause the monogenic autoinflammatory disease Deficiency in ELF4, X-linked (DEX), driven by aberrant inflammation. While it has been demonstrated by our lab that global loss of ELF4 results in hyper-cytokine release in macrophages and restrains Th17 differentiation in mice, the breadth and mechanisms of CD4+ T cell regulation by ELF4 remain enigmatic. Here, we show that loss of T cell-intrinsic ELF4 leads to enhanced interferon gamma and IL-17A production upon activation of naïve CD4+ T cells and demonstrate modulation of CD4+ T cell cytokine production by ELF4 is independent of its presence during T cell development as well as extrinsic signaling in vivo. Further, absence of T cell-intrinsic ELF4 leads to decreased expression of ATF4, a master regulator of the integrated stress response demonstrated to be crucial in restraining cytokine release upon initial activation of naïve T cells. Notably, we found ELF4 binds to the promoter region of ATF4, and expression of ATF4-induced genes is significantly reduced in CD4+ T cells in the absence of ELF4 post-activation. Thus, we elucidate an essential mechanism for restraining CD4+ T cell inflammatory potential dependent on regulation of the integrated stress response by ELF4.
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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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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".