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Chemokine decoy receptor D6 in inflammatory bowel disease (IBD) and IBD-associated colon cancer
  1. Colm B Collins,
  2. Eoin N McNamee,
  3. Joshua D Wermers,
  4. Matthew D P Lebsack,
  5. Jesús Rivera-Nieves
  1. Mucosal Inflammation Program, Division of Gastroenterology, Department of Internal Medicine, University of Colorado Health Sciences Center, Denver, Colorado, USA
  1. Correspondence to Jesús Rivera-Nieves, Mucosal Inflammation Program, University of Colorado Health Sciences Center, East 19th Ave 12700, MS B-146, RC2 Bldg Rm 10026, Aurora, CO 80045, USA; jesus.rivera-nieves{at}ucdenver.edu

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Thirteen years ago the first decoy receptor was identified (ie, IL-1 receptor type II). Lacking a cytoplasmic domain, it binds IL-1β, without triggering signal transduction. Thus the receptor was defined as “structurally incapable of transducing signal but able to recognise the agonist with high affinity and specificity”1 acting as a “sink” to prevent ligand activity. Since then, other cytokines and chemokines (mostly pro-inflammatory) have been found to be similarly regulated.2 Their mechanism of action is to compete with functional receptors for ligand binding and in some instances target the complex for degradation. Several decoy receptors for the chemokine family have been identified (eg, D6, DARC and CCXCKR). Common to all are mutations in or around the DRY motif that prevent G protein coupling and intracellular signal transduction.

D6 was first cloned in 19973 and its designation is that of the clone from which the cDNA was isolated (G Graham, personal communication, 13 August 2009). In D6 the DRYLAIV motif is replaced to DKYLEIV and just one substitution to DKYLAIV restores weak signal transduction capacity.4 D6 scavenges pro-inflammatory CC chemokines (ie, CCL2,3,4,7,8,11,13,17,22,23,24, CCL3L1) while sparing homeostatic CC chemokines, or those from other subfamilies.1 To accomplish this, D6 constitutively shuttles to and from the cell surface via recycling endosomes. Sensitive to the low pH of endosomes, internalised chemokines are released and degraded, allowing D6 to return to the cell surface, in a process …

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