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

Published online before print December 12, 2003
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1003473


Received for publication October 10, 2003.

Accepted for publication October 22, 2003.


Article

Extracellular and intracellular decoys in the tuning of inflammatory cytokines and Toll-like receptors: the new entry TIR8/SIGIRR

Alberto Mantovani *{dagger}@, Massimo Locati {dagger}, Nadia Polentarutti *, Annunciata Vecchi *, and Cecilia Garlanda *

*Department of Immunology and Cell Biology, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy; and {dagger}Centro di Eccellenza per l'Innovazione Diagnostica e Terapeutica (IDET) Institute of General Pathology, Faculty of Medicine, University of Milan, Italy

@ To whom correspondence should be addressed. E-mail: Mantovani{at}marionegri.it.


   Abstract

Following the identification of the interleukin (IL)-1 type II receptor as a prototypic decoy receptor, nonsignaling receptors with decoy functions have been identified for members of the IL-1/IL-18, tumor necrosis factor, IL-10, and IL-13 receptor families. Moreover, the silent receptor D6 is a promiscuous decoy and scavenger receptor of inflammatory chemokines. The type II IL-1 decoy receptor also acts as a dominant-negative molecule, and intracellular pathways of inhibition of IL-1 and Toll-like receptor (TLR) signaling have been identified. In particular, recent results suggest that the single immunoglobulin IL-1-related receptor family member translation initiation region 8 is a negative regulator of IL-1 and TLR signaling. Thus, extracellular and intracellular decoys tune the activation of members of the IL-1/TLR receptor family.

Key Words: osteoprotegerin • interleukin receptor antagonist • accessory protein




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