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Updated: Jan 16, 2026

SorLA and CLC:CLF-1-dependent Downregulation of CNTFRα as Demonstrated by Western Blotting, Inhibition of Lysosomal Enzymes, and Immunocytochemistry
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Cardiotrophin-like cytokine factor 1 forms a complex with IL12/IL23p40

Véronique Laplante1, Marine Rousseau2,3, Sonia Terki1

  • 1Département de pharmacologie et physiologie, Université de Montréal, Montréal, Québec, H3T 1J4, Canada.

Scientific Reports
|September 30, 2025
PubMed

Insights

Cardiotrophin-like cytokine factor 1 (CLCF1) interacts with p40, the IL12/IL23 beta subunit, forming a novel composite cytokine. This discovery sheds light on CLCF1's immune functions and potential roles in p40-related diseases.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cytokine Signaling

Background:

  • Cardiotrophin-like cytokine factor 1 (CLCF1) is a cytokine in the IL6/IL12 superfamily with known neurotrophic and immune functions.
  • CLCF1's neurotrophic effects are mediated by the ciliary neurotrophic factor receptor (CNTFR), but its immune-related receptor remains unidentified as CNTFRα is absent on immune cells.

Purpose of the Study:

  • To identify the alternative receptor or protein complex mediating the immune activities of CLCF1.
  • To investigate the interaction between CLCF1 and potential immune-related partners.

Main Methods:

  • BioID2 proximity-dependent biotinylation assay to identify CLCF1 interaction partners.
  • Co-immunoprecipitation and proximity ligation assay to confirm protein-protein interactions.
  • Analysis of CLCF1-p40 complex formation and secretion, including the role of CRLF1.

Main Results:

  • The p40 subunit (beta subunit of IL12/IL23) was identified as a CLCF1 interaction partner.
  • CLCF1 and p40 form a complex both intracellularly and extracellularly, with secretion induced by CRLF1, forming a tripartite complex.
  • A CLCF1-p40 fusion protein demonstrated binding to both CNTFRα and IL12Rβ1.

Conclusions:

  • A novel composite cytokine, CLCF1-p40, belonging to the IL6/IL12 superfamily, has been uncovered.
  • This finding may alter the understanding of CLCF1 functions and p40-associated pathologies.
  • The study reinforces the link between IL6 and IL12 cytokine families, suggesting further investigation into their interactions.

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