The Orphan Receptor CRF2-4 Is an Essential Subunit of the Interleukin 10 Receptor

نویسندگان

  • Susan D. Spencer
  • Francesco Di Marco
  • Jeff Hooley
  • Sharon Pitts-Meek
  • Michele Bauer
  • Anne M. Ryan
  • Bernard Sordat
  • Verna C. Gibbs
  • Michel Aguet
چکیده

The orphan receptor CRF2-4 is a member of the class II cytokine receptor family (CRF2), which includes the interferon receptors, the interleukin (IL) 10 receptor, and tissue factor. CRFB4, the gene encoding CRF2-4, is located within a gene cluster on human chromosome 21 that comprises three interferon receptor subunits. To elucidate the role of CRF2-4, we disrupted the CRFB4 gene in mice by means of homologous recombination. Mice lacking CRF2-4 show no overt abnormalities, grow normally, and are fertile. CRF2-4 deficient cells are normally responsive to type I and type II interferons, but lack responsiveness to IL-10. By approximately 12 wk of age, the majority of mutant mice raised in a conventional facility developed a chronic colitis and splenomegaly. Thus, CRFB4 mutant mice recapitulate the phenotype of IL-10-deficient mice. These findings suggest that CRF2-4 is essential for IL-10-mediated effects and is a subunit of the IL-10 receptor.

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عنوان ژورنال:
  • The Journal of Experimental Medicine

دوره 187  شماره 

صفحات  -

تاریخ انتشار 1998