Year: 2021
Type: article
Abstract: 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 (Nf1OPG) 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), Nf1OPG 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 Nf1OPG 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.
Source: Nature Communications
Institution: Washington University in St. Louis
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,560
Funders: U.S. Department of Health and Human Services, Alex's Lemonade Stand Foundation for Childhood Cancer, Foundation for Barnes-Jewish Hospital, Children's Discovery Institute, Georgia Clinical and Translational Science Alliance, National Institutes of Health, Center for Cellular Imaging, Washington University, National Heart, Lung, and Blood Institute, National Eye Institute, National Cancer Institute, National Institute of Neurological Disorders and Stroke, National Center for Research Resources, National Center for Advancing Translational Sciences
Awards: G1003443230, G1384259650, G1699415014, G261815350, G2824222223, G4069642107, G4103096715, G412336820, G4429321274, G4999255471, G5371549186, BASIC NEUROSCIENCES, G6096538348, G6120206497, G63402963, G6735790369, G7042258458, G8381610833, G9000006824, G9000037442, G9000051602, G9000133373, Defining and Controlling Airway Disease, Cancer Center Support Grant
OpenAlex ID: W4200550757