Treg cell-derived osteopontin promotes microglia-mediated white matter repair after ischemic stroke
- 이은엽
- 3월 30일
- 1분 분량
Immunity, Volume 54, Issue 7, 13 July 2021, Pages 1527-1542.e8
작성자: 이은엽
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 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.
Treg cells 가 뇌졸중 회복에 미치는 유익한 효과의 메커니즘은 여전히 불분명하지만 뇌에 침투하는 Treg cells가 뇌졸중 후 뇌 회복을 향상시킨다.
Treg cells에서 유래한 osteopontin은 tissue-reparative microglial의 반응을 촉진하여 뇌졸중의 만성 단계에서 oligodendrocyte regeneration과 remyelination를 촉진한다. IL-2:IL-2 항체 복합체로 Treg cell의 수를 늘리면 장기적인 뇌졸중 회복이 개선된다
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