Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Chatterjee, Jit, Sanapala, Shilpa, Cobb, Olivia, Bewley, Alice, Goldstein, Andrea K., Cordell, Elizabeth, Ge, Xia, Garbow, Joel R., Holtzman, Michael J., Gutmann, David H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8654836/
https://www.ncbi.nlm.nih.gov/pubmed/34880260
http://dx.doi.org/10.1038/s41467-021-27455-6
_version_ 1784611950709178368
author Chatterjee, Jit
Sanapala, Shilpa
Cobb, Olivia
Bewley, Alice
Goldstein, Andrea K.
Cordell, Elizabeth
Ge, Xia
Garbow, Joel R.
Holtzman, Michael J.
Gutmann, David H.
author_facet Chatterjee, Jit
Sanapala, Shilpa
Cobb, Olivia
Bewley, Alice
Goldstein, Andrea K.
Cordell, Elizabeth
Ge, Xia
Garbow, Joel R.
Holtzman, Michael J.
Gutmann, David H.
author_sort Chatterjee, Jit
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8654836
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-86548362021-12-27 Asthma reduces glioma formation by T cell decorin-mediated inhibition of microglia Chatterjee, Jit Sanapala, Shilpa Cobb, Olivia Bewley, Alice Goldstein, Andrea K. Cordell, Elizabeth Ge, Xia Garbow, Joel R. Holtzman, Michael J. Gutmann, David H. Nat Commun Article 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. Nature Publishing Group UK 2021-12-08 /pmc/articles/PMC8654836/ /pubmed/34880260 http://dx.doi.org/10.1038/s41467-021-27455-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Chatterjee, Jit
Sanapala, Shilpa
Cobb, Olivia
Bewley, Alice
Goldstein, Andrea K.
Cordell, Elizabeth
Ge, Xia
Garbow, Joel R.
Holtzman, Michael J.
Gutmann, David H.
Asthma reduces glioma formation by T cell decorin-mediated inhibition of microglia
title Asthma reduces glioma formation by T cell decorin-mediated inhibition of microglia
title_full Asthma reduces glioma formation by T cell decorin-mediated inhibition of microglia
title_fullStr Asthma reduces glioma formation by T cell decorin-mediated inhibition of microglia
title_full_unstemmed Asthma reduces glioma formation by T cell decorin-mediated inhibition of microglia
title_short Asthma reduces glioma formation by T cell decorin-mediated inhibition of microglia
title_sort asthma reduces glioma formation by t cell decorin-mediated inhibition of microglia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8654836/
https://www.ncbi.nlm.nih.gov/pubmed/34880260
http://dx.doi.org/10.1038/s41467-021-27455-6
work_keys_str_mv AT chatterjeejit asthmareducesgliomaformationbytcelldecorinmediatedinhibitionofmicroglia
AT sanapalashilpa asthmareducesgliomaformationbytcelldecorinmediatedinhibitionofmicroglia
AT cobbolivia asthmareducesgliomaformationbytcelldecorinmediatedinhibitionofmicroglia
AT bewleyalice asthmareducesgliomaformationbytcelldecorinmediatedinhibitionofmicroglia
AT goldsteinandreak asthmareducesgliomaformationbytcelldecorinmediatedinhibitionofmicroglia
AT cordellelizabeth asthmareducesgliomaformationbytcelldecorinmediatedinhibitionofmicroglia
AT gexia asthmareducesgliomaformationbytcelldecorinmediatedinhibitionofmicroglia
AT garbowjoelr asthmareducesgliomaformationbytcelldecorinmediatedinhibitionofmicroglia
AT holtzmanmichaelj asthmareducesgliomaformationbytcelldecorinmediatedinhibitionofmicroglia
AT gutmanndavidh asthmareducesgliomaformationbytcelldecorinmediatedinhibitionofmicroglia