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

Jit Chatterjee, Shilpa Sanapala, Olivia Cobb, Alice Bewley, Andrea K. Goldstein, Elizabeth Cordell, Xia Ge, Joel R. Garbow, Michael J. Holtzman and David H. Gutmann ()
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Jit Chatterjee: Washington University School of Medicine
Shilpa Sanapala: Washington University School of Medicine
Olivia Cobb: Washington University School of Medicine
Alice Bewley: Washington University School of Medicine
Andrea K. Goldstein: Washington University School of Medicine
Elizabeth Cordell: Washington University School of Medicine
Xia Ge: Washington University School of Medicine
Joel R. Garbow: Washington University School of Medicine
Michael J. Holtzman: Washington University School of Medicine
David H. Gutmann: Washington University School of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-27455-6

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