Asthma reduces glioma formation by T cell decorin-mediated inhibition of microglia.
Jit ChatterjeeShilpa SanapalaOlivia CobbAlice BewleyAndrea K GoldsteinElizabeth CordellXia GeJoel R GarbowMichael J HoltzmanDavid H GutmannPublished in: Nature communications (2021)
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.
Keyphrases
- signaling pathway
- lps induced
- inflammatory response
- nuclear factor
- chronic obstructive pulmonary disease
- pi k akt
- lung function
- allergic rhinitis
- oxidative stress
- optic nerve
- poor prognosis
- neuropathic pain
- endothelial cells
- young adults
- liver fibrosis
- optical coherence tomography
- liver injury
- risk factors
- gene expression
- risk assessment
- artificial intelligence
- cystic fibrosis
- human health
- spinal cord injury
- type diabetes
- metabolic syndrome
- big data
- climate change
- machine learning