| Literature DB >> 34015256 |
Ligen Shi1, Zeyu Sun1, Wei Su1, Fei Xu2, Di Xie1, Qingxiu Zhang1, Xuejiao Dai1, Kartik Iyer1, T Kevin Hitchens3, Lesley M Foley3, Sicheng Li1, Donna B Stolz4, Kong Chen5, Ying Ding6, Angus W Thomson7, Rehana K Leak8, Jun Chen2, Xiaoming Hu9.
Abstract
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 to 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.Entities:
Keywords: microglia; oligodendrocytes; osteopontin; regulatory T cells; stroke recovery; white matter
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Year: 2021 PMID： 34015256 PMCID： PMC8282725 DOI： 10.1016/j.immuni.2021.04.022
Source DB: PubMed Journal: Immunity ISSN： 1074-7613 Impact factor: 43.474