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

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.

• Authors: Jit Chatterjee, Shilpa Sanapala, Olivia Cobb, Alice Bewley, Andrea K Goldstein, Elizabeth Cordell, Xia Ge, Joel R Garbow, Michael J Holtzman, David H Gutmann
• Journal: Nature communications (Nat Commun) Vol. 12 Issue 1 Pg. 7122 (12 08 2021) ISSN: 2041-1723 [Electronic] England
• PMID: 34880260 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s).

Chemical References

• Ccl4 protein, mouse
• Ccl5 protein, mouse
• Chemokine CCL4
• Chemokine CCL5
• Decorin
• Neurofibromin 1

Topics

• Animals
• Asthma (immunology, metabolism)
• Brain Neoplasms (pathology)
• Chemokine CCL4 (metabolism)
• Chemokine CCL5 (metabolism)
• Decorin (metabolism)
• Disease Models, Animal
• Glioma
• Mice
• Mice, Inbred C57BL
• Microglia (metabolism)
• Monitoring, Immunologic
• Neurofibromatosis 1 (metabolism)
• Neurofibromin 1 (genetics, metabolism)
• Optic Nerve (metabolism)
• Optic Nerve Glioma (pathology)
• Signal Transduction
• T-Lymphocytes (immunology)