Leukotriene B4 receptor 1 expression on dendritic cells is required for the development of Th2 responses and allergen-induced airway hyperresponsiveness.
Dendritic cells (DC) are important APCs that control allergen-induced airway responses by interacting directly with T cells. Leukotriene B(4) (LTB(4)), interacting with its high-affinity receptor, LTB(4) receptor 1 (BLT1), is known to attract and activate leukocytes during inflammation. We have previously shown that BLT1 expression on Ag-primed T cells is required for the development of airway hyperresponsiveness (AHR; Miyahara et al. 2005. Am. J. Respir. Crit. Care Med. 172: 161-167). However, the role for the LTB(4)-BLT1 pathway in DC function in allergen-induced airway responses has not been defined. Bone marrow-derived DCs (BMDC) were generated. Naive BALB/c mice received OVA-pulsed BLT1-deficient (BLT1(-/-)) BMDCs or wild-type BMDCs intratracheally and were then challenged with OVA for 3 days. Airway responses were monitored 48 h after the last allergen challenge. BLT1(-/-) BMDCs showed normal maturation judged from surface expression of CD markers. Compared with recipients of wild-type BMDCs, mice that received BLT1(-/-) BMDCs developed significantly lower AHR to inhaled methacholine, lower goblet cell metaplasia, and eosinophilic infiltration in the airways and decreased levels of Th2 type cytokines in the bronchoalveolar lavage fluid. Migration of BLT1(-/-) BMDCs into peribronchial lymph nodes was significantly impaired compared with BLT1(+/+) BMDCs after intratracheal instillation. These data suggest that BLT1 expression on DCs is required for migration of DCs to regional lymph nodes as well as in the development of AHR and airway inflammation.
Miyahara
Nobuaki
N
Department of Pediatrics, Division of Cell Biology, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Ohnishi
Hiroshi
H
Matsuda
Hiroyuki
H
Miyahara
Satoko
S
Takeda
Katsuyuki
K
Koya
Toshiyuki
T
Matsubara
Shigeki
S
Okamoto
Masakazu
M
Dakhama
Azzeddine
A
Haribabu
Bodduluri
B
Gelfand
Erwin W
EW
D000485:Allergens / Q000276:immunology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage; D016207:Cytokines / Q000032:analysis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D017572:Leukotriene A4 / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D016210:Methacholine Chloride / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D018102:Receptors, Leukotriene B4 / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
D000485:Allergens; D016085:Bronchoconstrictor Agents; D016207:Cytokines; D017572:Leukotriene A4; C503704:Ltb4r1 protein, mouse; D018102:Receptors, Leukotriene B4; D016210:Methacholine Chloride; D010047:Ovalbumin