Asthma reduces glioma formation by T cell decorin-mediated inhibition of microglia.
Asthma reduces glioma formation by T cell decorin-mediated inhibition of microglia.
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哮喘通过T细胞decorin介导的小胶质细胞抑制减少胶质瘤的形成。
DOI：
10.1038/s41467-021-27455-6
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发表时间：
2021-12-08
影响因子：
16.6
通讯作者：
Gutmann DH
中科院分区：
文献类型：
--
作者：
Chatterjee J;Sanapala S;Cobb O;Bewley A;Goldstein AK;Cordell E;Ge X;Garbow JR;Holtzman MJ;Gutmann DH
为了阐明1型神经纤维瘤病（NF1）和哮喘患儿脑肿瘤发病率降低的机制，我们利用NF1视神经胶质瘤（Nf1OPG）小鼠、人和小鼠RNAseq数据以及两种不同的实验性哮喘模型。在4-6周龄（WOA）诱导卵清蛋白或屋尘螨哮喘后，Nf1OPG小鼠视神经体积和增殖在12和24 WOA时下降，表明没有肿瘤发展。这种抑制伴随着小胶质细胞产生的视神经胶质瘤有丝分裂原Ccl5的表达减少。人和小鼠T细胞转录组分析显示，抑制小胶质细胞Ccl5的产生是由于T细胞decorin表达的增加，decorin通过减少小胶质细胞NFκB信号传导来阻断ccl4介导的小胶质细胞Ccl5表达。在4-6 WOA时对Nf1OPG小鼠进行Decorin或NFκB抑制剂治疗，可抑制12 WOA时的肿瘤形成，从而为哮喘患儿胶质瘤发病率降低建立了潜在的机制病因。临床研究表明，患有哮喘的儿童患脑肿瘤（包括视神经胶质瘤）的几率降低。在1型神经纤维瘤病相关的低级别视神经胶质瘤小鼠模型中，作者发现实验性哮喘诱导减少了胶质瘤的形成和生长，这是由于T细胞依赖性抑制了小胶质细胞介导的肿瘤支持。
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. Clinical studies have suggested a reduced incidence of brain tumors, including optic gliomas, in children with asthma. Here, in a mouse model of Neurofibromatosis type 1 associated low grade optic glioma, the authors show that experimental asthma induction decreases glioma formation and growth, resulting from T cell-dependent inhibition of microglia-mediated tumor support.
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影响因子：
3.7
作者：
Koerner-Rettberg C;Doths S;Stroet A;Schwarze J
通讯作者：
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影响因子：
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影响因子：
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作者：
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通讯作者：
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影响因子：
2.3
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