美国国立卫生研究院Keisuke Nagao团队发现，内肽酶ADAM10-Notch信号轴的中断导致皮肤菌群失调和先天淋巴细胞介导的毛囊破坏。相关论文于2021年9月27日在线发表在《免疫》杂志上。

研究人员发现上层毛囊（HF）中跨膜内肽酶ADAM10的表达对于调节皮肤微生物群和保护HF及其干细胞微环境免受炎症破坏至关重要。ADAM10-Notch信号轴的敲减损害了先天性上皮屏障，并使柯氏杆菌在微生物群中占主导地位。菌群失调以白细胞介素-7（IL-7）受体、S1P受体1和CCR6依赖的方式引发了第2组先天淋巴细胞介导的炎症，导致HF的焦亡和不可逆转的脱发。

双链RNA诱导的敲减模型表明，ADAM10-Notch信号轴通过促进I型干扰素反应下游的β-防御素-6表达来增强上皮的先天免疫力。因此，ADAM10-Notch信号轴介导的宿主-微生物共生的调节，关键是保护HF免受炎症破坏，这对慢性炎症期间维持组织的完整性有意义。

据介绍，HF作为干细胞、免疫细胞和共生微生物的枢纽，在平衡状态和短暂的炎症期间必须受到严格的监管。

附：英文原文

Title: Disruption of the endopeptidase ADAM10-Notch signaling axis leads to skin dysbiosis and innate lymphoid cell-mediated hair follicle destruction

Author: Keiko Sakamoto, Seon-Pil Jin, Shubham Goel, Jay-Hyun Jo, Benjamin Voisin, Doyoung Kim, Vinod Nadella, Hai Liang, Tetsuro Kobayashi, Xin Huang, Clay Deming, Keisuke Horiuchi, Julia A. Segre, Heidi H. Kong, Keisuke Nagao

Issue&Volume: 2021-09-27

Abstract: Hair follicles (HFs) function as hubs for stem cells, immune cells, and commensalmicrobes, which must be tightly regulated during homeostasis and transient inflammation.Here we found that transmembrane endopeptidase ADAM10 expression in upper HFs wascrucial for regulating the skin microbiota and protecting HFs and their stem cellniche from inflammatory destruction. Ablation of the ADAM10-Notch signaling axis impairedthe innate epithelial barrier and enabled Corynebacterium species to predominate the microbiome. Dysbiosis triggered group 2 innate lymphoidcell-mediated inflammation in an interleukin-7 (IL-7) receptor-, S1P receptor 1-,and CCR6-dependent manner, leading to pyroptotic cell death of HFs and irreversiblealopecia. Double-stranded RNA-induced ablation models indicated that the ADAM10-Notchsignaling axis bolsters epithelial innate immunity by promoting β-defensin-6 expressiondownstream of type I interferon responses. Thus, ADAM10-Notch signaling axis-mediatedregulation of host-microbial symbiosis crucially protects HFs from inflammatory destruction,which has implications for strategies to sustain tissue integrity during chronic inflammation.

DOI: 10.1016/j.immuni.2021.09.001

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00364-2