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長庚大學 臨床醫學研究所

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大師學術演講系列 - Akihiko Yoshimura, Ph.D.

Regulatory T cells and ischemic brain injury

Akihiko Yoshimura
Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan

Regulatory T cells (Tregs) play a central role in maintaining immune homeostasis, and the Forkhead transcription factor, Foxp3 defines the Treg cell lineage and functions. Various transcription factors and epigenetic regulation are involved in Treg development and functions. We discovered that Nr4a transcription factors are necessary for the Treg development in the thymus and stability at the periphery (1). The Nr4a factors are shown to be involved not only in Treg development but also in the anergy and exhaustion of T cells (2). Tregs are expected for immunotherapy of various immunological diseases and suppression of rejection of organ transplantation (3).
In addition to conventional functions of immunological suppression, Tregs have been shown to exhibit tissue-specific functions that contribute to tissue homeostasis and repair (4). We recently discovered that Tregs accumulate in the brain at the chronic phase of ischemic brain injury (5). Gene expression analysis revealed that brain Tregs were related to Tregs in other tissues such as adipose tissue and muscle, however, brain Tregs expressed several unique genes related to the nervous system including serotonin receptor, Htr7. Brain Tregs regulate astrocyte activation and reduce neural damages by producing EGF-like molecule, Amphiregulin. Our findings suggest that Tregs and their products may provide new therapeutic opportunities for neuronal protection against stroke.

(1) Sekiya et al. Nat Immunol. 2013, 14(3):230-7.
(2) Chen et al. Nature. 2019, 567(7749):530-534.
(3) Kasahara et al. Int Immunol. 2017, 29(10):457-469.
(4) Ito et al. Int Immunol. 2019; 31(6):361-369.
(5) Ito et al. Nature. 2019, 565(7738):246-250.
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