Work

Pulmonary lymphangiogenesis promotes lung B cell responses and bronchus-associated lymphoid tissue (BALT) initiation in chronic allergic asthma 2744

Year: 2025

Type: article

Abstract: Description Bronchus-associated lymphoid tissue (BALT) is associated with severe asthma; however, its initiation is incompletely understood. In chronic lung infection models, lymphangiogenesis (LAG), driven by VEGF-C/VEGFR-3 signaling, occurs near BALT-rich areas; nonetheless, a causative link has remained elusive. Here, we asked whether LAG promotes BALT in chronic asthma. First, we examined samples from fatal asthmatic donors and found that serum VEGF-C positively correlated with BALT and serum IgE. To assess a causative role for LAG in BALT initiation, we used genetic and pharmacological methods to control VEGFR-3 signaling in mouse models of asthma. We found that enhanced pulmonary LAG promoted BALT initiation and increased IgE, while blocking reduced such. BALT supported lung (but not lymph node) B cell responses, including local germinal center reactions and immunoglobulin class-switching. The increases in BALT and IgE were lymphatic endothelial cell (LEC)-specific, as mice lacking VEGFR-3 on LECs were protected from these phenomena. In chronic allergy, lung LECs upregulate CXCL13, and its expression was necessary in the VEGF-C mediated BALT exacerbations. Finally, we identified BALT-disrupting therapeutic targets, as the use of blocking antibodies ameliorated BALT and respiratory B cell burden in mice subjected to allergic airway disease. Altogether, our results suggest a causative role for pulmonary LECs in initiating BALT and supporting lung B cell responses in allergic asthma. Funding Sources Supported by NIH/NIAID R21 AI130821, NIH/NCI R01 CA219304 NIH/NCI R01 CA253248, and the Chicago Immunoengineering Innovation Center. Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.630