Repopulating Microglia Promote Brain Repair in an IL-6-Dependent Manner

被引：388

作者：

Willis, Emily F. ^{[1
,2
]}

MacDonald, Kelli P. A. ^{[3
]}

Nguyen, Quan H. ^{[4
]}

Garrido, Adahir Labrador ^{[1
]}

Gillespie, Ellen R. ^{[1
]}

Harley, Samuel B. R. ^{[1
,2
]}

Bartlett, Perry F. ^{[2
]}

Schroder, Wayne A. ^{[3
,7
]}

Yates, Abi G. ^{[5
]}

Anthony, Daniel C. ^{[5
]}

Rose-John, Stefan ^{[6
]}

Ruitenberg, Marc J. ^{[1
]}

Vukovic, Jana ^{[1
,2
]}

机构：

[1] Univ Queensland, Fac Med, Sch Biomed Sci, Brisbane, Qld, Australia

[2] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia

[3] QIMR Berghofer Med Res Inst, Dept Immunol, Brisbane, Qld, Australia

[4] Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia

[5] Univ Oxford, Dept Pharmacol, Lab Expt Neuropathol, Oxford OX1 3QT, England

[6] Christian Albrechts Univ Kiel, Biochem Inst, Kiel, Germany

[7] Griffith Univ, Sch Environm & Sci, Brisbane, Qld, Australia

来源：

CELL | 2020年 / 180卷 / 05期

基金：

澳大利亚研究理事会; 英国医学研究理事会; 澳大利亚国家健康与医学研究理事会;

关键词：

PROGENITOR-CELL; STEM-CELLS; IN-VIVO; INTERLEUKIN-6; NEURONS; INFLAMMATION; INJURY; DEGENERATION; REVEALS; DOUBLECORTIN;

D O I：

10.1016/j.cell.2020.02.013

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Cognitive dysfunction and reactive microglia are hallmarks of traumatic brain injury (TBI), yet whether these cells contribute to cognitive deficits and secondary inflammatory pathology remains poorly understood. Here, we show that removal of microglia from the mouse brain has little effect on the outcome of TBI, but inducing the turnover of these cells through either pharmacologic or genetic approaches can yield a neuroprotective microglial phenotype that profoundly aids recovery. The beneficial effects of these repopulating microglia are critically dependent on interleukin-6 (IL-6) trans-signaling via the soluble IL-6 receptor (IL-6R) and robustly support adult neurogenesis, specifically by augmenting the survival of newborn neurons that directly support cognitive function. We conclude that microglia in the mammalian brain can be manipulated to adopt a neuroprotective and pro-regenerative phenotype that can aid repair and alleviate the cognitive deficits arising from brain injury.

引用

页码：833 / +

页数：30

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