Journal Article

Asthma reduces glioma formation by T cell decorin-mediated inhibition of microglia

Ge, Xia, Garbow, Joel R., Chatterjee, Jit, Sanapala, Shilpa, Cobb, Olivia, Holtzman, Michael J., Bewley, Alice, Cordell, Elizabeth, Gutmann, David H., Goldstein, Andrea K.

2021

Overview

To elucidate the mechanisms underlying the reduced incidence of brain tumors in children with Neurofibromatosis type 1 (NF1) and asthma, we leverage Nf1 optic pathway glioma ( Nf1 OPG ) mice, human and mouse RNAseq data, and two different experimental asthma models. Following ovalbumin or house dust mite asthma induction at 4–6 weeks of age (WOA), Nf1 OPG mouse optic nerve volumes and proliferation are decreased at 12 and 24 WOA, indicating no tumor development. This inhibition is accompanied by reduced expression of the microglia-produced optic glioma mitogen, Ccl5. Human and murine T cell transcriptome analyses reveal that inhibition of microglia Ccl5 production results from increased T cell expression of decorin, which blocks Ccl4-mediated microglia Ccl5 expression through reduced microglia NFκB signaling. Decorin or NFκB inhibitor treatment of Nf1 OPG mice at 4–6 WOA inhibits tumor formation at 12 WOA, thus establishing a potential mechanistic etiology for the attenuated glioma incidence observed in children with asthma. Clinical studies have suggested a reduced incidence of brain tumors, including optic gliomas, in children with asthma. Here, in a mouse model of Neurofibromatosis type 1 associated low grade optic glioma, the authors show that experimental asthma induction decreases glioma formation and growth, resulting from T cell-dependent inhibition of microglia-mediated tumor support.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 14 / 14/34 / 14/63 / 45 / 45/91 / 631/67/1922 / 631/67/2332 / 631/67/580/1884 / 64 / 64/60 / 82/80 / Animal models / Animals / Asthma / Asthma - immunology / Asthma - metabolism / Brain / Brain cancer / Brain Neoplasms - pathology / Brain tumors / Chemokine CCL4 - metabolism / Chemokine CCL5 - metabolism / Children / Decorin / Decorin - metabolism / Disease Models, Animal / Etiology / Genetic disorders / Glioma / Glioma cells / House dust / Humanities and Social Sciences / Lymphocytes / Lymphocytes T / Mice / Mice, Inbred C57BL / Microglia / Microglia - metabolism / Monitoring, Immunologic / multidisciplinary / Neurofibromatosis / Neurofibromatosis 1 - metabolism / Neurofibromin 1 - genetics / Neurofibromin 1 - metabolism / Neurological disorders / NF-κB protein / Optic nerve / Optic Nerve - metabolism / Optic Nerve Glioma - pathology / Ovalbumin / Recklinghausen's disease / Science / Science (multidisciplinary) / Signal Transduction / T-Lymphocytes - immunology / Transcriptomes / Tumors