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Cited by 422

The DOI matches its Crossref record; 78 of the 78 references it cites were found in a registry or an index.

Treg cell-derived osteopontin promotes microglia-mediated white matter repair after ischemic stroke

Open access
Shi, Ligen, Sun, Zeyu, Su, Wei, Xu, Fei, Xie, Di, Zhang, Qingxiu, Dai, Xuejiao, Iyer, Kartik, Hitchens, T. Kevin, Foley, Lesley M., Li, Sicheng, Stolz, Donna B., Chen, Kong, Ding, Ying, Thomson, Angus W., Leak, Rehana K., Chen, Jun, Hu, Xiaoming·2021·Immunity

Abstract

Summary: 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.

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Metadata

Authors
Shi, L., Sun, Z., Su, W., Xu, F., Xie, D., Zhang, Q., Dai, X., Iyer, K., Hitchens, T. K., Foley, L. M., Li, S., Stolz, D. B., Chen, K., Ding, Y., Thomson, A. W., Leak, R. K., Chen, J., & Hu, X.
Venue
Immunity
Publisher
Elsevier BV
Published
2021-07
Volume
54
Issue
7
Pages
1527-1542.e8
ISSN
1074-7613 (ISSN-L)
OpenAlex
W3163657510
Cited by
422
References
78
FWCI
21.49
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Treg cell-derived osteopontin promotes microglia-mediated white matter repair after ischemic stroke. https://app.cochat.ai/papers/10.1016/j.immuni.2021.04.022
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Shi, L., Sun, Z., Su, W., Xu, F., Xie, D., Zhang, Q., Dai, X., Iyer, K., Hitchens, T. K., Foley, L. M., Li, S., Stolz, D. B., Chen, K., Ding, Y., Thomson, A. W., Leak, R. K., Chen, J., & Hu, X. (2021). Treg cell-derived osteopontin promotes microglia-mediated white matter repair after ischemic stroke. Immunity. https://doi.org/10.1016/j.immuni.2021.04.022

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.