Requirement for chemokine receptor 5 in the development of allergen-induced airway hyperresponsiveness and inflammation

Yasuko Fuchimoto, Arihiko Kanehiro, Nobuaki Miyahara, Hikari Koga, Genyo Ikeda, Koichi Waseda, Yasushi Tanimoto, Satoshi Ueha, Mikio Kataoka, Erwin W. Gelfand, Mitsune Tanimoto

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Chemokine receptor (CCR) 5 is expressed on dendritic cells, macrophages, CD8 cells, memory CD4 T cells, and stromal cells, and is frequently used as a marker of T helper type 1 cells. Interventions that abrogate CCR5 or interfere with its ligand binding have been shown to alter T helper type 2-induced inflammatory responses. The role of CCR5 on allergic airway responses is not defined. CCR5-deficient (CCR5 -/-) and wild-type (CCR5 +/+) mice were sensitized and challenged with ovalbumin (OVA) and allergic airway responses were monitored 48 hours after the last OVA challenge. Cytokine levels in lung cell culture supernatants were also assessed. CCR5 -/- mice showed significantly lower airway hyperresponsiveness (AHR) and lower numbers of total cells, eosinophils, and lymphocytes in bronchoalveolar lavage (BAL) fluid compared with CCR5 +/+ mice after sensitization and challenge. The levels of IL-4 and IL-13 in BAL fluid of CCR5 -/- mice were lower than in CCR5 +/+ mice. Decreased numbers of lung T cells were also detected in CCR5 -/- mice after sensitization and challenge. Transfer of OVA-sensitized T cells from CCR5 +/+, but not transfer of CCR5 -/- cells, into CCR5 -/- mice restored AHR and numbers of eosinophils in BAL fluid after OVA challenge. Accordingly, the numbers of airway-infiltrating donor T cells were significantly higher in the recipients of CCR5 +/+ T cells. Taken together, these data suggest that CCR5 plays a pivotal role in allergen-induced AHR and airway inflammation, and that CCR5 expression on T cells is essential to the accumulation of these cells in the airways.

Original languageEnglish
Pages (from-to)1248-1255
Number of pages8
JournalAmerican journal of respiratory cell and molecular biology
Volume45
Issue number6
DOIs
Publication statusPublished - Dec 1 2011

    Fingerprint

Keywords

  • Chemokines
  • Cytokines
  • Lung
  • Rodent
  • T cells

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Cite this

Fuchimoto, Y., Kanehiro, A., Miyahara, N., Koga, H., Ikeda, G., Waseda, K., Tanimoto, Y., Ueha, S., Kataoka, M., Gelfand, E. W., & Tanimoto, M. (2011). Requirement for chemokine receptor 5 in the development of allergen-induced airway hyperresponsiveness and inflammation. American journal of respiratory cell and molecular biology, 45(6), 1248-1255. https://doi.org/10.1165/rcmb.2010-0465OC