Leukotriene B4 receptor 1 expression on dendritic cells is required for the development of Th2 responses and allergen-induced airway hyperresponsiveness

Nobuaki Miyahara, Hiroshi Ohnishi, Hiroyuki Matsuda, Satoko Miyahara, Katsuyuki Takeda, Toshiyuki Koya, Shigeki Matsubara, Masakazu Okamoto, Azzeddine Dakhama, Bodduluri Haribabu, Erwin W. Gelfand

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Abstract

Dendritic cells (DC) are important APCs that control allergen-induced airway responses by interacting directly with T cells. Leukotriene B4 (LTB4), interacting with its high-affinity receptor, LTB4 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 LTB4-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.

Original languageEnglish
Pages (from-to)1170-1178
Number of pages9
JournalJournal of Immunology
Volume181
Issue number2
DOIs
Publication statusPublished - Jul 15 2008

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Miyahara, N., Ohnishi, H., Matsuda, H., Miyahara, S., Takeda, K., Koya, T., Matsubara, S., Okamoto, M., Dakhama, A., Haribabu, B., & Gelfand, E. W. (2008). Leukotriene B4 receptor 1 expression on dendritic cells is required for the development of Th2 responses and allergen-induced airway hyperresponsiveness. Journal of Immunology, 181(2), 1170-1178. https://doi.org/10.4049/jimmunol.181.2.1170