Increased inflammation in mice deficient for the chemokine decoy receptor D6

Yeny Martinez de la Torre, Massimo Locati, Chiara Buracchi, Jana Dupor, Donald N. Cook, Raffaella Bonecchi, Manuela Nebuloni, Daniel Rukavina, Luca Vago, Annunciata Vecchi, Sergio A. Lira, Alberto Mantovani

Research output: Contribution to journalArticle

Abstract

Chemokines are chemotactic cytokines with a key role in the control of cell trafficking and positioning under homeostatic and inflammatory conditions. D6 is a promiscuous 7-transmembrane-domain receptor expressed on lymphatic vessels which recognizes most inflammatory, but not homeostatic, CC chemokines. In vitro experiments demonstrated that D6 is unable to signal after ligand engagement, and it is structurally adapted to sustain rapid and efficient ligand internalization and degradation. These unique functional properties lead to the hypothesis that D6 may be involved in the control of inflammation by acting as a decoy and scavenger receptor for inflammatory chemokines. Consistent with this hypothesis, here we report that D6-/-mice showed an anticipated and exacerbated inflammatory response in a model of skin inflammation. Moreover, the absence of D6 resulted in increase cellularity and inflammatory-chemokine levels in draining lymph nodes. Thus, D6 is a decoy receptor structurally adapted and strategically located to tune tissue inflammation and control transfer of inflammatory chemokines to draining lymph nodes.

Original languageEnglish
Pages (from-to)1342-1346
Number of pages5
JournalEuropean Journal of Immunology
Volume35
Issue number5
DOIs
Publication statusPublished - May 2005

Keywords

  • Chemokine receptors
  • Chemokines
  • Decoy receptors
  • Inflammation
  • Lymphatic endothelium

ASJC Scopus subject areas

  • Immunology

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  • Cite this

    de la Torre, Y. M., Locati, M., Buracchi, C., Dupor, J., Cook, D. N., Bonecchi, R., Nebuloni, M., Rukavina, D., Vago, L., Vecchi, A., Lira, S. A., & Mantovani, A. (2005). Increased inflammation in mice deficient for the chemokine decoy receptor D6. European Journal of Immunology, 35(5), 1342-1346. https://doi.org/10.1002/eji.200526114