이은엽
2021년 6월 1일
- Treg cells가 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
https://doi.org/10.1016/j.immuni.2021.04.022
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.
