2019 Fiscal Year Annual Research Report

皮内の制御性Ｔ細胞による皮膚免疫応答制御機構の解明

Research Project

Project/Area Number	18F18096
Research Institution	Kyoto University
Principal Investigator	椛島健治京都大学, 医学研究科, 教授 (00362484)
Co-Investigator(Kenkyū-buntansha)	CHOW ZACHARY 京都大学, 医学(系)研究科(研究院), 外国人特別研究員
Project Period (FY)	2018-04-25 – 2020-03-31
Keywords	メラノサイト / 白斑 / 神経 / Regulatory T Cell / Two photon microscopy / Contact Hypersensitivity / Dermal dendritic cell / iSALT
Outline of Annual Research Achievements	The purpose of this research is to further understand regulatory T cell (Tregs) function in the skin during steady state and inflammatory conditions. Briefly, Treg behavior was visualized via a two-photon microscope in the ear skin of a live mouse using various Treg-specific fluorescent reporter mice during the contact hypersensitivity skin inflammatory response. Treg colocalization and interactions with dermal dendritic cells (DCs) was investigated via immunohistochemistry, and the combination of Treg and DC reporter mice. The Treg-Cre recombinase mouse (Foxp3-Cre) was also crossed with a R26-LSL-Gi-DREADD mouse to enable chemical inactivation of chemokine signaling to inhibit Treg migration in the skin. However issues with stochastic activity in the Foxp3-Cre mouse rendered the newly generated mouse unreliable as Gi-DREADD insertion was no longer Treg specific. While studying the relationship between sensory nerves and the immune system, we made a novel observation that chemical denervation with resiniferatoxin (RTX) induced hair loss in mice. Subsequent regrown hair in these bald areas were permenantly pigmented, suggesting a dysfunction in melanocyte stem cells of the affected hair follicles. As Tregs are known to reside around the hair follicle and support hair follicle cycling, we depleted Tregs prior to and during RTX-administration. Surprisingly, Treg-depleted mice had delayed hair regrowth, but regrown hair was still depigmented. This suggests that while Tregs may be important for hair follicle stem cells, they do not affect melanocyte stem cells in the follicle.
Research Progress Status	令和元年度が最終年度であるため、記入しない。
Strategy for Future Research Activity	令和元年度が最終年度であるため、記入しない。