Pulmonary lymphatic endothelial cells mediate induction of bronchus associated lymphoid tissue in chronic allergic asthma.

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B842
Abstract ID: 4147

Presenting Author:
Jorge E Gomez Medellin , Postdoctoral scholar at Univ. of Chicago Pritzker Sch. of Molecular Engr.

Abstract:

Patients with allergic asthma exhibit airway inflammation due to immune hyperresponsiveness to respiratory allergens. Previous reports suggest a high prevalence of vascular endothelial growth factors (VEGFs) in asthmatic sera. Here, we asked what role does the lymphangiogenic VEGF-C plays in allergic asthma. In asthmatic sera, VEGF-C levels positively correlated with IgE, and fatal asthmatic lung samples presented with a higher extent of bronchus associated lymphoid tissue (BALT). In this study, we used mouse models of allergic airway inflammation to probe if VEGF-C increases IgE levels in chronic allergy. Here, we demonstrated that VEGF-C driven pulmonary lymphangiogenesis promotes BALT and IgE. Using pharmacological agents and transgenic mouse models, we determined that VEGF receptor (VEGFR)-3 expressed by lymphatic endothelial cells (LECs) is necessary to mediate BALT. Furthermore, expansion of the pulmonary lymphatic vasculature predisposes the lung microenvironment to develop BALT upon chronic allergen inhalation. In response to chronic allergy, pulmonary LECs upregulate the B lymphocyte chemoattractant CXCL13, and its expression was necessary in the VEGF-C mediated BALT exacerbations. Finally, the use of CXCL13 blocking antibodies ameliorated BALT, identifying a potential therapeutic target for patients suffering from allergic asthma. Altogether, our results suggest a causative role for pulmonary LECs in mediating BALT in chronic allergy through expression of CXCL13.