Athymic mice reveal a requirement for T-cell-microglia interactions in establishing a microenvironment supportive of Nf1 low-grade glioma growth

被引：53

作者：

Pan, Yuan ^{[1
]}

Xiong, Min ^{[1
,2
]}

Chen, Ran ^{[1
]}

Ma, Yu ^{[1
]}

Corman, Courtney ^{[1
]}

Maricos, Meron ^{[3
]}

Kindler, Urs ^{[3
]}

Semtner, Marcus ^{[3
]}

Chen, Yi-Hsien ^{[1
,4
]}

Dahiya, Sonika ^{[5
]}

Gutmann, David H. ^{[1
]}

机构：

[1] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA

[2] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Reprod Med Ctr, Wuhan 430030, Hubei, Peoples R China

[3] Max Delbruck Ctr Mol Med Helmholtz Assoc MDC, Cellular Neurosci, D-13125 Berlin, Germany

[4] Washington Univ, Sch Med, GEIC, St Louis, MO 63110 USA

[5] Washington Univ, Sch Med, Div Neuropathol, St Louis, MO 63110 USA

来源：

GENES & DEVELOPMENT | 2018年 / 32卷 / 7-8期

基金：

美国国家卫生研究院;

关键词：

tumor microenvironment; stroma; monocyte; chemokines; OPTIC-GLIOMA; PILOCYTIC ASTROCYTOMA; STEM-CELLS; MOUSE; INACTIVATION; ACTIVATION; DRIVES;

D O I：

10.1101/gad.310797.117

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Pediatric low-grade gliomas (LGGs) frequently do not engraft in immunocompromised mice, limiting their use as an experimental platform. In contrast, murine Neuro-fibromatosis- 1 (Nf1) optic LGG stem cells (o-GSCs) form glioma-like lesions in wild-type, but not athymic, mice following transplantation. Here, we show that the inability of athymic mice to support o-GSC engraftment results from impaired microglia/macrophage function, including reduced expression of Ccr2 and Ccl5, both of which are required for o-GSC engraftment and Nf1 optic glioma growth. Impaired Ccr2 and Ccl5 expression in athymic microglia/macrophages was restored by T-cell exposure, establishing T-cell-microglia/macrophage interactions as critical stromal determinants that support NF1 LGG growth.

引用

页码：491 / 496

页数：6

共 34 条

[1] Human FOXN1-Deficiency Is Associated with αβ Double-Negative and FoxP3+T-Cell Expansions That Are Distinctly Modulated upon Thymic Transplantation [J].

Albuquerque, Adriana S. ;

Marques, Jose G. ;

Silva, Susana L. ;

Ligeiro, Dario ;

Devlin, Blythe H. ;

Dutrieux, Jacques ;

Cheynier, Remi ;

Pignata, Claudio ;

Victorino, Rui M. M. ;

Markert, M. Louise ;

Sousa, Ana E. .

PLOS ONE, 2012, 7 (05)

[2]

Bajenaru ML, 2003, CANCER RES, V63, P8573

[3]

Carson MJ, 1999, J NEUROSCI RES, V55, P127, DOI 10.1002/(SICI)1097-4547(19990101)55:1<127::AID-JNR14>3.3.CO

[4]

2-U

[5]

Chabot S, 1999, J IMMUNOL, V162, P6819

[6] Cytokine production in T lymphocyte-microglia interaction is attenuated by glatiramer acetate: a mechanism for therapeutic efficacy in multiple sclerosis [J].

Chabot, S ;

Yong, FP ;

Le, DM ;

Metz, LM ;

Myles, T ;

Yong, VW .

MULTIPLE SCLEROSIS JOURNAL, 2002, 8 (04) :299-306

[7] CCL2 Produced by the Glioma Microenvironment Is Essential for the Recruitment of Regulatory T Cells and Myeloid-Derived Suppressor Cells [J].

Chang, Alan L. ;

Miska, Jason ;

Wainwright, Derek A. ;

Dey, Mahua ;

Rivetta, Claudia V. ;

Yu, Dou ;

Kanojia, Deepak ;

Pituch, Katarzyna C. ;

Qiao, Jian ;

Pytel, Peter ;

Han, Yu ;

Wu, Meijing ;

Zhang, Lingjiao ;

Horbinski, Craig M. ;

Ahmed, Atique U. ;

Lesniak, Maciej S. .

CANCER RESEARCH, 2016, 76 (19) :5671-5682

[8] Mouse Low-Grade Gliomas Contain Cancer Stem Cells with Unique Molecular and Functional Properties [J].

Chen, Yi-Hsien ;

McGowan, Lucy D'Agostino ;

Cimino, Patrick J. ;

Dahiya, Sonika ;

Leonard, Jeffrey R. ;

Lee, Da Yong ;

Gutmann, David H. .

CELL REPORTS, 2015, 10 (11) :1899-1912

[9] Cellular and Molecular Identity of Tumor-Associated Macrophages in Glioblastoma [J].

Chen, Zhihong ;

Feng, Xi ;

Herting, Cameron J. ;

Garcia, Virginia Alvarez ;

Nie, Kai ;

Pong, Winnie W. ;

Rasmussen, Rikke ;

Dwivedi, Bhakti ;

Seby, Sandra ;

Wolf, Susanne A. ;

Gutmann, David H. ;

Hambardzumyan, Dolores .

CANCER RESEARCH, 2017, 77 (09) :2266-2278

[10] Neurofibromatosis-1 (Nf1) heterozygous brain microglia elaborate paracrine factors that promote Nf1-deficient astrocyte and glioma growth [J].

Daginakatte, Girish C. ;

Gutmann, David H. .

HUMAN MOLECULAR GENETICS, 2007, 16 (09) :1098-1112

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