NLRC5 Limits the Activation of Inflammatory Pathways
Why this work is in the frame
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Bibliographic record
Abstract
Nod-like receptors (NLRs) are intracellular sentinel proteins that are implicated in the detection of microbes and danger signals, thereby controlling several key innate immune pathways. The human genome encodes 22 NLR proteins, the function of many of which remains unknown. In this study, we present the identification and characterization of NLRC5, a NLR protein whose expression is found predominantly in cells of the myeloid and lymphoid lineages. NLRC5 expression was strongly induced by IFN-gamma and more modestly by LPS and polyinosinic:polycytidylic acid. Overexpression of NLRC5 in HEK293T cells resulted in a global dampening of NF-kappaB-, AP-1-, and type I IFN-dependent signaling, most likely through transcriptional repression. Accordingly, NLRC5 was found to shuttle between the cytosol and the nucleus in a CrmA-dependent manner. Knocking down NLRC5 expression in RAW264.7 murine macrophages resulted in a potent upregulation of the proinflammatory responses to IFN-gamma and LPS, including increased secretion of TNF, IL-6, and IL-1beta, as well as cell surface expression of CD40. Strikingly, NLRC5 expression was also found to be critical for LPS-induced IL-10 production in RAW264.7 macrophages. Collectively, our results identify NLRC5 as a negative modulator of inflammatory pathways.
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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 | 0.000 |
| 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 it