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A critical role for VEGF secreted by Dendritic cells (DCs) in priming T helper 2 (Th2) development in response to specific stimuli
Author(s) -
Krishnamoorthy Nandini,
Oriss Timothy,
Paglia Melissa,
Fei Mingjian,
Ray Anuradha,
Ray Prabir
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.670.8
Subject(s) - priming (agriculture) , immunology , immune system , downregulation and upregulation , vascular endothelial growth factor , angiogenesis , aspergillus fumigatus , biology , medicine , cancer research , vegf receptors , biochemistry , botany , germination , gene
Asthma is an inflammatory disease of the small airways caused by an exaggerated CD4 Th2 response. We have shown that OVA coupled with cholera toxin (CT) when administered intranasally into mice recapitulate the hallmarks of asthma. In vitro, CT ‐treated Dcs prime naïve T cells towards a Th2 response. We undertook a microarray approach to dissect the mechanism of CT‐ induced Th2 response. Our microarray data revealed upregulation of expression of vascular endothelial growth factor (VEGF) by CT in DCs. Recently, a novel role for VEGF as a mediator of Th2 immune responses has been reported. In accordance with our microarray data, CT induced secretion of VEGF in tissue and bone marrow DCs. Interestingly, we have found that allergens selectively induce VEGF expression in DCs despite their common ability to promote allergic diseases. Aspergillus fumigatus, the causative agent of allergic bronchopulmonary aspergillosis, induced VEGF production from DCs but house dust mite did not. We also found that VEGF secreted by DCs was critical for the differentiation of Th2 cells. We show that iNOS and NF‐kappa B enhance the production of VEGF from DCs, in contrast to inhibition by IL‐12. We also show the Th2‐ priming ability of DCs to be compromised in iNOS −/− mice. In summary, our study underscores the complexity of Th2 responses by highlighting a previously unknown but essential pathway via DC‐derived VEGF in response to specific stimuli.