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Pro-lymphangiogenic VEGFR-3 signaling modulates memory T cell responses in allergic airway inflammation

In allergic airway inflammation, VEGFR-3-mediated lymphangiogenesis occurs in humans and mouse models, yet its immunological roles, particularly in adaptive immunity, are poorly understood. Here, we explored how pro-lymphangiogenic signaling affects the allergic response to house dust mite (HDM). In...

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Detalles Bibliográficos
Autores principales: Maisel, Katharina, Hrusch, Cara L., Medellin, Jorge E. G., Potin, Lambert, Chapel, David B., Nurmi, Harri, Camacho, Daniel F., Gleyzer, Rachel, Alitalo, Kari, Sperling, Anne I., Swartz, Melody A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725864/
https://www.ncbi.nlm.nih.gov/pubmed/32518367
http://dx.doi.org/10.1038/s41385-020-0308-4
Descripción
Sumario:In allergic airway inflammation, VEGFR-3-mediated lymphangiogenesis occurs in humans and mouse models, yet its immunological roles, particularly in adaptive immunity, are poorly understood. Here, we explored how pro-lymphangiogenic signaling affects the allergic response to house dust mite (HDM). In the acute inflammatory phase, the lungs of mice treated with blocking antibodies against VEGFR-3 (mF4-31C1) displayed less inflammation overall, with dramatically reduced innate and T cell numbers and reduced inflammatory chemokine levels. However, when inflammation was allowed to resolve and memory recall was induced 2 months later, mice treated with mF4-31C1 as well as VEGF-C/-D knockout models showed exacerbated type 2 memory response to HDM, with increased Th2 cells, eosinophils, type 2 chemokines, and pathological inflammation scores. This was associated with lower CCL21 and decreased T(Regs) in the lymph nodes. Together, our data imply that VEGFR-3 activation in allergic airways both help initiate the acute inflammatory response as well as regulate the adaptive (memory) response, possibly in part by shifting the T(Reg)/Th2 balance. This introduces new immunomodulatory roles for pro-lymphangiogenic VEGFR-3 signaling in allergic airway inflammation and suggests that airway lymphatics may be a novel target for treating allergic responses.