Resident human dermal γδT-cells operate as stress-sentinels: Lessons from the hair follicle
Resident human dermal γδT-cells operate as stress-sentinels: Lessons from the hair follicle
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人类真皮常驻 γδT 细胞充当压力哨兵：来自毛囊的教训
DOI：
10.1016/j.jaut.2021.102711
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发表时间：
2021
期刊：
影响因子：
12.8
通讯作者：
Kanekura T,
中科院分区：
文献类型：
--
作者：
Uchida Y;Gherardini J;Pappelbaum K;Cheret J;Schulte-Mecklenbeck A;Gross C;Strbo N;Gilhar A;Kanekura T,
小鼠γδ t细胞具有应激监视功能，并与自身免疫有关。然而，人类γδ t细胞是否也是应激哨兵并直接促进皮肤的自身免疫反应尚不清楚。使用一种新的（微型）器官试验，我们测试了人类真皮驻留的γδ t细胞是否可以识别应激的人类头皮毛囊（HFs），从而促进斑秃（AA）样自身免疫反应。因此，我们发现来自健康人头皮皮肤的γδ t细胞被激活（CD69+），上调NKG2D和IFN-γ的表达，并在与自体应激HFsex体内共培养时具有细胞毒性。这些自体γδ t细胞诱导HF免疫特权崩溃、营养不良和过早退化，即人类自身免疫性HF疾病AA的三个标志。这是由CXCL12、MICA介导的，部分由IFN-γ和CD1d介导。总之，人皮肤γδ t细胞在人体皮肤中发挥生理应激前哨功能，其过度活性可以促进对过度表达CD1d， CXCL12和/或MICA的应激HFs的自身免疫。
Murine γδT-cells have stress-surveillance functions and are implicated in autoimmunity. Yet, whether human γδT-cells are also stress sentinels and directly promote autoimmune responses in the skin is unknown. Using a novel (mini-)organ assay, we tested if human dermis resident γδT-cells can recognize stressed human scalp hair follicles (HFs) to promote an alopecia areata (AA)-like autoimmune response. Accordingly, we show that γδT-cells from healthy human scalp skin are activated (CD69+), up-regulate the expression of NKG2D and IFN-γ, and become cytotoxic when co-cultured with autologous stressed HFsex vivo. These autologous γδT-cells induce HF immune privilege collapse, dystrophy, and premature catagen, i.e. three hallmarks of the human autoimmune HF disorder, AA. This is mediated by CXCL12, MICA, and in part by IFN-γ and CD1d. In conclusion, human dermal γδT-cells exert physiological stress-sentinel functions in human skin, where their excessive activity can promote autoimmunity towards stressed HFs that overexpress CD1d, CXCL12, and/or MICA.