| First Author | Shi L | Year | 2021 |
| Journal | Immunity | Volume | 54 |
| Issue | 7 | Pages | 1527-1542.e8 |
| PubMed ID | 34015256 | Mgi Jnum | J:348725 |
| Mgi Id | MGI:6740294 | Doi | 10.1016/j.immuni.2021.04.022 |
| Citation | Shi L, et al. (2021) Treg cell-derived osteopontin promotes microglia-mediated white matter repair after ischemic stroke. Immunity 54(7):1527-1542.e8 |
| abstractText | 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. |
