Journal of Leukocyte Biology Myeloid cells, immune suppression, tumor immunology
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A more recent version of this article appeared on August 1, 2004

Published online before print May 3, 2004
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0204117

Received for publication February 27, 2004.
Revised April 8, 2004.
Accepted for publication April 9, 2004.

Article

The expanded family of class II cytokines that share the IL-10 receptor-2 (IL-10R2) chain

Raymond P. Donnelly *@, Faruk Sheikh *, Sergei V. Kotenko {dagger}, and Harold Dickensheets *

*Division of Therapeutic Proteins, Center for Drug Evaluation & Research, Food and Drug Administration, Bethesda, Maryland; and {dagger}Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry of New Jersey, Newark

@ To whom correspondence should be addressed. E-mail: donnelly{at}cber.fda.gov.


  Abstract

Several novel interleukin (IL)-10-related cytokines have recently been discovered. These include IL-22, IL-26, and the interferon-{lambda} (IFN-{lambda}) proteins IFN-{lambda}1 (IL-29), IFN-{lambda}2 (IL-28A), and IFN-{lambda}3 (IL-28B). The ligand-binding chains for IL-22, IL-26, and IFN-{lambda} are distinct from that used by IL-10; however, all of these cytokines use a common second chain, IL-10 receptor-2 (IL-10R2; CRF2-4), to assemble their active receptor complexes. Thus, IL-10R2 is a shared component in at least four distinct class II cytokine-receptor complexes. IL-10 binds to IL-10R1; IL-22 binds to IL-22R1; IL-26 binds to IL-20R1; and IFN-{lambda} binds to IFN-{lambda}R1 (also known as IL-28R). The binding of these ligands to their respective R1 chains induces a conformational change that enables IL-10R2 to interact with the newly formed ligand-receptor complexes. This in turn activates a signal-transduction cascade that results in rapid activation of several transcription factors, particularly signal transducer and activator of transcription (STAT)3 and to a lesser degree, STAT1. Activation by IL-10, IL-22, IL-26, or IFN-{lambda} can be blocked with neutralizing antibodies to the IL-10R2 chain. Although IL-10R2 is broadly expressed on a wide variety of tissues, only a subset of these tissues expresses the ligand-binding R1 chains. The receptors for these cytokines are often present on cell lines derived from various tumors, including liver, colorectal, and pancreatic carcinomas. Consequently, the receptors for these cytokines may provide novel targets for inhibiting the growth of certain types of cancer.

Key Words: IFN-{lambda} • STAT3/STAT1 • NK cell






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Copyright © 2004 by the Society for Leukocyte Biology.