Suppressive role of neuroimmune semaphorin 4A in allergen-induced and VEGF-regulated lung inflammatory responses

Abstract

Event Abstract Back to Event Suppressive role of neuroimmune semaphorin 4A in allergen-induced and VEGF-regulated lung inflammatory responses Svetlana P. Chapoval1*, Elizabeth Smith2, EusebiusHenri Nkyimbeng-Takwi1, Kathleen Shanks1, Michael M. Lipsky3, Louis J. DeTolla3, Jack A. Elias4 and Achsah D. Keegan5 1 University of Maryland, Department of Microbiology and Immunology, Center for Vascular and Inflammatory Diseases, Program in Oncology at Greenebaum Cancer Center, United States 2 University of Maryland School of Medicine, Center for Vascular and Inflammatory Diseases, United States 3 University of Maryland School of Medicine, Department of Pathology, United States 4 Yale University School of Medicine, Medicine, United States 5 University of Maryland School of Medicine, Department of Microbiology and Immunology, Center for Vascular and Inflammatory Diseases, Program in Oncology at Greenebaum Cancer Center, United States Asthma-relevant responses can be induced by innate (VEGF, TSLP) as well as adaptive stimuli (allergens). Our studies of VEGF lung overexpressor transgenic (tg) mice highlighted the mechanisms by which innate immune stimuli can predispose the lung to Th2 sensitization (Lee CG et al., Nat Med, 2004, 10:1095-1103; Chapoval SP et al., Clin Immunol, 2009, 132:371-384). Our study on allergen administration to Sema4A-/- mice provided a new insight into the lung immune semaphorin biology and Th2 inflammatory response regulation (Nkyimbeng-Takwi EH et al., Mucosal Immunol, 2012, 5:409-419). We have shown that Sema4A-/- mice displayed a more robust allergic response as compared to WT mice. This included selective increases in eosinophilic airway infiltration, bronchial epithelial cell hyperplasia, AHR, and BAL IL-13 content but lower Treg numbers. We recently generated VEGF tg/Sema4A-/- mice and assessed the effect of Sema4A deficiency on VEGF tg lung tissue phenotype. As we have shown previously, lung bronchial epithelial expression of VEGF transgene lead to an asthma-like phenotype with inflammation, parenchymal remodeling, increased vascularization, edema formation, mucous cell and myocyte hyperplasia and airway hyperreactivity. The observed lung tissue inflammatory response and vascularization in VEGF tg/Sema4A-/- mice were more pronounced than those found in tg mice alone. In addition, similarly to allergen-treated Sema4A-/- mice, we observed higher local levels of IL-13 in VEGF tg mice with Sema4A deficiency. Thus, Sema4A downregulates both innate and adaptive lung allergic responses. The new knowledge obtained from this study will be used for the development of optimal strategies for asthma intervention. Acknowledgements We thank Prof. Hitoshi Kikutani (Osaka University, Japan) for providing us Sema4A-deficient mice. This work was supported by NIH/NIAID R21 AI076736 (S.P.C.). Keywords: Sema4A, allergen, VEGF, Asthma, Inflammation Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Immune-mediated disease pathogenesis Citation: Chapoval SP, Smith E, Nkyimbeng-Takwi E, Shanks K, Lipsky MM, DeTolla LJ, Elias JA and Keegan AD (2013). Suppressive role of neuroimmune semaphorin 4A in allergen-induced and VEGF-regulated lung inflammatory responses. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00718 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 13 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Svetlana P Chapoval, University of Maryland, Department of Microbiology and Immunology, Center for Vascular and Inflammatory Diseases, Program in Oncology at Greenebaum Cancer Center, Baltimore, MD, 21201, United States, schapoval@som.umaryland.edu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Svetlana P Chapoval Elizabeth Smith EusebiusHenri Nkyimbeng-Takwi Kathleen Shanks Michael M Lipsky Louis J DeTolla Jack A Elias Achsah D Keegan Google Svetlana P Chapoval Elizabeth Smith EusebiusHenri Nkyimbeng-Takwi Kathleen Shanks Michael M Lipsky Louis J DeTolla Jack A Elias Achsah D Keegan Google Scholar Svetlana P Chapoval Elizabeth Smith EusebiusHenri Nkyimbeng-Takwi Kathleen Shanks Michael M Lipsky Louis J DeTolla Jack A Elias Achsah D Keegan PubMed Svetlana P Chapoval Elizabeth Smith EusebiusHenri Nkyimbeng-Takwi Kathleen Shanks Michael M Lipsky Louis J DeTolla Jack A Elias Achsah D Keegan Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.