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Distinct Roles of Vascular Endothelial Growth Factor Receptor-1-and Receptor-2-Mediated Signaling in T Cell Priming and Th17 Polarization to Lipopolysaccharide-Containing Allergens in the Lung

Title
Distinct Roles of Vascular Endothelial Growth Factor Receptor-1-and Receptor-2-Mediated Signaling in T Cell Priming and Th17 Polarization to Lipopolysaccharide-Containing Allergens in the Lung
Authors
Kim, YSChoi, SJTae, YMLee, BJJeon, SGOh, SYGho, YSZhu, ZKim, YK
POSTECH Authors
Gho, YS
Date Issued
Nov-2010
Publisher
AMER ASSOC IMMUNOLOGISTS
Abstract
Vascular endothelial growth factor (VEGF) is a key mediator in the development of airway immune dysfunction to inhaled allergens. However, the exact role of its receptors-mediated signaling is controversial. In this study, we evaluated the role of VEGF receptor (VEGFR)-1- and VEGFR-2-mediated signaling in T cell priming and polarization in the context of inhalation of LPS-containing allergens. A murine asthma model of mixed Th1 and Th17 cell responses was generated using intranasal sensitization with LPS-containing allergens. Pharmacologic intervention was performed during sensitization. In vivo production of VEGF and Th1- and Th17-polarizing cytokines (IL-12p70 and IL-6, respectively) were upregulated by airway exposure to LPS. Pharmacological intervention with a VEGFR-2-neutralizing Ab (anti-Flk1 mAb) abolished the production of IL-6 (but not IL-12p70) and the subsequent development of allergen-specific Th17 cell response. On the other hand, blocking VEGFR-1 signaling with a VEGFR-1 antagonist (anti-Flt1 hexapeptide) did not affect the production of IL-12p70 and IL-6. However, blocking VEGFR-1 signaling resulted in T cell tolerance rather than priming, mainly by inhibiting the maturation of lung dendritic cells, and their migration into lung-draining lymph nodes. These results suggest that T cell priming to LPS-containing allergens depends on VEGFR-1-mediated signaling, and the subsequent Th17 polarization depends on VEGFR-2 signaling. The Journal of Immunology, 2010, 185: 5648-5655.
Keywords
DENDRITIC CELL; FACTOR VEGF; EXPERIMENTAL ASTHMA; LYMPH-NODES; EXPRESSION; AIRWAYS; ANGIOGENESIS; MATURATION; MIGRATION; RESPONSES
URI
http://oasis.postech.ac.kr/handle/2014.oak/25588
DOI
10.4049/JIMMUNOL.1001713
ISSN
0022-1767
Article Type
Article
Citation
JOURNAL OF IMMUNOLOGY, vol. 185, no. 9, page. 5648 - 5655, 2010-11
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 GHO, YONG SONG
Dept of Life Sciences
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