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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.

Authors: Kim, YS  Choi, SJ  Tae, YM  Lee, BJ  Jeon, SG  Oh, SY  Gho, YS  Zhu, Z  Kim, YK 
Citation: Kim YS, etal., J Immunol. 2010 Nov 1;185(9):5648-55. Epub 2010 Oct 4.
Pubmed: (View Article at PubMed) PMID:20921519
DOI: Full-text: DOI:10.4049/jimmunol.1001713

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.


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CRRD Object Information
CRRD ID: 5684385
Created: 2011-12-19
Species: All species
Last Modified: 2011-12-19
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.