Characterization of a new cytokine complex from the IL-6/IL-12 family
Bibliographic record
Abstract
Abstract Cardiotrophin-like cytokine factor 1 (CLCF1) is a neurotrophic factor initially identified as a B lymphocyte stimulating factor. Mutations in CLCF1 cause type 2 Cold-Induced Sweating Syndrome, a severe multisystem disorder coupled with recurrent childhood infections. The CLCF1-CRLF1 composite cytokine mediate its neurotrophic effects via the CNTF receptor (CNTFR). Although immune cells do not express CNTFR, immunological activities of CLCF1 have been described, suggesting the existence of an alternative receptor. Preliminary results suggest that CLCF1 can associate with the Epstein-Barr virus-induced gene 3(EBI3). EBI3 is a subunit of the composite cytokines IL-27, IL-35 and IL-39, which exhibits immunoregulatory functions. Our hypothesis is that CLCF1 associates with EBI3 to activate an alternative receptor expressed by immune cells. The aim of the project is to identify the cells producing CLCF1/EBI3, to define its receptor and to characterize the influence of CLCF1/EBI3 on lymphocyte proliferation, differentiation, and function. We find that EBI3 and CLCF1 subunits can associate extracellularly to form a CLCF1/EBI3 complex. Moreover, we uncovered that this complex can bind to IL-12Rß1, IL-23R and CNTFRα receptor chains. Altogether, our data strongly suggest that the CLCF1/EBI3 complex is likely to assemble in vivo and act as a cytokine through known receptor chains. Overall, defining the cellular targets and biological activities of CLCF1/EBI3 will pave the way for the development of treatments in autoimmune diseases involving CLCF1 and EBI3, adding to the increasing number of biologic drugs targeting cytokines, their receptors, or signaling pathways that are used clinically to treat inflammatory diseases. Supported by IRSC (RNI00404)
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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) | 0.001 | 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".