Cardiotrophin-like cytokine factor 1 forms a complex with IL12/IL23p40
Bibliographic record
Abstract
Cardiotrophin-like cytokine factor 1 (CLCF1) is a cytokine of the IL6/IL12 superfamily with pro-neurotrophic and immune-modulating functions. Although the pro-neurotrophic activities of CLCF1 are mediated through the ciliary neurotrophic factor receptor (CNTFR), the α receptor chain of the CNTFR, CNTFRα, is not expressed by immune cells. This suggests the presence of an alternative receptor or protein complex that mediates the immune activities of CLCF1. Using the BioID2 proximity-dependent biotinylation assay, we identified p40, the β subunit of IL12/IL23, as a potential interaction partner for CLCF1. We confirmed the protein-protein interaction between CLCF1 and p40 using co-immunoprecipitation and a proximity ligation assay. We also observed that the CLCF1-p40 complex forms both intracellularly and in the extracellular space. Furthermore, secretion of the CLCF1-p40 heterodimer was induced by the cytokine receptor-like factor 1 (CRLF1), leading to the release of a tripartite CLCF1-CRLF1-p40 complex. Lastly, we showed that a CLCF1-p40 fusion protein binds to both CNTFRα and IL12Rβ1. Taken together, our results uncover a new putative composite cytokine of the IL6/IL12 superfamily, which might affect our understanding of both CLCF1 activities and p40-associated pathologies. Moreover, our results reinforce the connection between the IL6 and IL12 cytokine families, and suggest that other possible protein interactions between these two families should be further investigated.
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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".