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 language | English |
|---|---|
| Pages (from-to) | 1248-1255 |
| Number of pages | 8 |
| Journal | American Journal of Respiratory Cell and Molecular Biology |
| Volume | 45 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Dec 1 2011 |
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Keywords
- Chemokines
- Cytokines
- Lung
- Rodent
- T cells
ASJC Scopus subject areas
- Cell Biology
- Pulmonary and Respiratory Medicine
- Molecular Biology
- Clinical Biochemistry
Cite this
Requirement for chemokine receptor 5 in the development of allergen-induced airway hyperresponsiveness and inflammation. / Fuchimoto, Yasuko; Kanehiro, Arihiko; Miyahara, Nobuaki; Koga, Hikari; Ikeda, Genyo; Waseda, Koichi; Tanimoto, Yasushi; Ueha, Satoshi; Kataoka, Mikio; Gelfand, Erwin W.; Tanimoto, Mitsune.
In: American Journal of Respiratory Cell and Molecular Biology, Vol. 45, No. 6, 01.12.2011, p. 1248-1255.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Requirement for chemokine receptor 5 in the development of allergen-induced airway hyperresponsiveness and inflammation
AU - Fuchimoto, Yasuko
AU - Kanehiro, Arihiko
AU - Miyahara, Nobuaki
AU - Koga, Hikari
AU - Ikeda, Genyo
AU - Waseda, Koichi
AU - Tanimoto, Yasushi
AU - Ueha, Satoshi
AU - Kataoka, Mikio
AU - Gelfand, Erwin W.
AU - Tanimoto, Mitsune
PY - 2011/12/1
Y1 - 2011/12/1
N2 - 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.
AB - 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.
KW - Chemokines
KW - Cytokines
KW - Lung
KW - Rodent
KW - T cells
UR - http://www.scopus.com/inward/record.url?scp=82755192555&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=82755192555&partnerID=8YFLogxK
U2 - 10.1165/rcmb.2010-0465OC
DO - 10.1165/rcmb.2010-0465OC
M3 - Article
VL - 45
SP - 1248
EP - 1255
JO - American Journal of Respiratory Cell and Molecular Biology
JF - American Journal of Respiratory Cell and Molecular Biology
SN - 1044-1549
IS - 6
ER -