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Identification and functional characterization of a second chain of the interleukin-10 receptor complex

S V Kotenko1, C D Krause, L S Izotova

  • 1Department of Molecular Genetics and Microbiology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ 08854-5635, USA.

The EMBO Journal
|October 6, 1997
PubMed

Insights

Interleukin-10 (IL-10) signaling requires a second receptor chain, CRFB4 (IL-10R2), in addition to the previously known IL-10R1 chain. This accessory chain is essential for IL-10 to initiate signal transduction events.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • Interleukin-10 (IL-10) is a critical cytokine regulating immune responses.
  • IL-10 exerts its effects through a cell surface receptor complex.
  • Previously, only the IL-10Ralpha (IL-10R1) ligand-binding chain was identified.

Purpose of the Study:

  • To identify the complete functional receptor complex for Interleukin-10 (IL-10).
  • To elucidate the role of previously uncharacterized proteins in IL-10 signal transduction.

Main Methods:

  • Co-expression of IL-10R1 and CRFB4 in hamster cells.
  • Ligand binding assays with human IL-10.
  • Chemical cross-linking to detect IL-10:CRFB4 complexes.
  • Co-immunoprecipitation studies using peripheral blood mononuclear cells.

Main Results:

  • Human IL-10 bound to IL-10R1 but did not induce signaling in its absence.
  • Co-expression of CRFB4 rendered cells sensitive to IL-10, indicating CRFB4 is essential for IL-10 signal transduction.
  • Direct evidence of IL-10:CRFB4 complex formation was observed.
  • CRFB4 was co-immunoprecipitated with IL-10R1 in human cells treated with IL-10.

Conclusions:

  • The CRFB4 chain, designated IL-10R2 or IL-10Rbeta, is a crucial component of the functional IL-10 receptor.
  • CRFB4 acts as an accessory chain, essential for initiating IL-10-induced signal transduction.
  • This discovery completes the characterization of the active IL-10 receptor complex.

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