RGD Reference Report - 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.

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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.
RGD ID:	5684385
Pubmed:	PMID:20921519 (View Abstract at PubMed)
DOI:	DOI:10.4049/jimmunol.1001713 (Journal Full-text)
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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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
asthma		ISO	Kdr (Mus musculus)	5684385; 5684385		RGD
asthma		IMP		5684385		RGD

Objects Annotated

Genes (Rattus norvegicus)

Kdr (kinase insert domain receptor)

Genes (Mus musculus)

Kdr (kinase insert domain protein receptor)

Genes (Homo sapiens)

KDR (kinase insert domain receptor)

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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.