Treg cell-derived osteopontin promotes microglia-mediated white matter repair after ischemic stroke.
Treg cell-derived osteopontin promotes microglia-mediated white matter repair after ischemic stroke.
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DOI：
10.1016/j.immuni.2021.04.022
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发表时间：
2021-07-13
期刊：
影响因子：
32.4
通讯作者：
Hu X
中科院分区：
文献类型：
--
作者：
Shi L;Sun Z;Su W;Xu F;Xie D;Zhang Q;Dai X;Iyer K;Hitchens TK;Foley LM;Li S;Stolz DB;Chen K;Ding Y;Thomson AW;Leak RK;Chen J;Hu X
调节性T(Treg)细胞在长期组织修复中的有益作用的确切机制仍然不清楚。在这里，使用单细胞RNA测序和流式细胞术，我们发现在实验性中风小鼠1-5周后Treg细胞渗入脑组织。选择性去除Treg细胞会减少卒中后少突胶质细胞的形成、白质修复和功能恢复。转录分析显示，大脑浸润性Treg细胞对包括单核细胞系细胞在内的其他免疫细胞具有强大的免疫调节作用。小胶质细胞的耗尽，而不是T细胞的淋巴细胞减少，减轻了转移的Treg细胞对白质再生的有利影响。在机制上，Treg细胞来源的骨桥蛋白通过小胶质细胞上的整合素受体作用于小胶质细胞，增强小胶质细胞的修复活性，从而促进少突胶质细胞的形成和白质修复。卒中后通过传递IL-2：IL-2抗体复合体来增加Treg细胞数量，改善了白质完整性，并从长期来看挽救了神经功能。这些发现表明，Treg细胞是中风康复的神经恢复靶点。Treg细胞对中风康复的有益作用的潜在机制尚不清楚。Shih等人。有报道称，脑部渗透的Treg细胞可促进中风后的大脑修复。Treg细胞来源的骨桥蛋白促进组织修复的小胶质细胞反应，从而促进中风慢性期的少突胶质细胞再生和再髓鞘形成。使用IL-2：IL-2抗体复合体提高Treg细胞数量可改善中风的长期康复。
The precise mechanisms underlying the beneficial effects of regulatory T (Treg) cells on long-term tissue repair remain elusive. Here, using single-cell RNA sequencing and flow cytometry, we found that Treg cells infiltrated the brain 1–5 weeks after experimental stroke in mice. Selective depletion of Treg cells diminished oligodendrogenesis, white matter repair, and functional recovery after stroke. Transcriptomic analyses revealed potent immunomodulatory effects of brain-infiltrating Treg cells on other immune cells, including monocyte-lineage cells. Microglia depletion, but not T cell lymphopenia, mitigated the beneficial effects of transferred Treg cells on white matter regeneration. Mechanistically, Treg cell-derived osteopontin acted through integrin receptors on microglia to enhance microglial reparative activity, consequently promoting oligodendrogenesis and white matter repair. Increasing Treg cell numbers by delivering IL-2:IL-2 antibody complexes after stroke improved white matter integrity and rescued neurological functions over the long term. These findings reveal Treg cells as a neurorestorative target for stroke recovery. The mechanisms underlying the beneficial effects of Treg cells on stroke recovery remain unclear. Shi et al. report that brain-infiltrating Treg cells enhance brain repair after stroke. Treg cell-derived osteopontin promotes a tissue-reparative microglial response, thereby facilitating oligodendrocyte regeneration and remyelination at the chronic stages of stroke. Boosting Treg cell numbers with an IL-2:IL-2 antibody complex improves long-term stroke recovery.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
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通讯作者：
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影响因子：
82.9
作者：
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影响因子：
25
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DOI：
10.1083/jcb.200308101
发表时间：
2004-01-05
期刊：
The Journal of cell biology
影响因子：
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作者：
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通讯作者：
Gage FH
DOI：
10.1093/brain/awr074
发表时间：
2011-05
期刊：
Brain : a journal of neurology
影响因子：
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作者：
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通讯作者：
Appel SH