Disruption of the endopeptidase ADAM10-Notch signaling axis leads to skin dysbiosis and innate lymphoid cell-mediated hair follicle destruction.
Disruption of the endopeptidase ADAM10-Notch signaling axis leads to skin dysbiosis and innate lymphoid cell-mediated hair follicle destruction.
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DOI：
10.1016/j.immuni.2021.09.001
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发表时间：
2021-10-12
期刊：
影响因子：
32.4
通讯作者：
Nagao K
中科院分区：
文献类型：
--
作者：
Sakamoto K;Jin SP;Goel S;Jo JH;Voisin B;Kim D;Nadella V;Liang H;Kobayashi T;Huang X;Deming C;Horiuchi K;Segre JA;Kong HH;Nagao K
毛囊（HF）是干细胞、免疫细胞和毛囊微生物的枢纽，在稳态和短暂炎症期间必须受到严格调控。在这里，我们发现，在上部HFs中的跨膜内肽酶ADAM 10表达对于调节皮肤微生物群和保护HFs及其干细胞生态位免受炎症破坏至关重要。ADAM 10-Notch信号传导轴的消融损害了先天上皮屏障，并使棒状杆菌属物种能够主导微生物组。生态失调以IL-7受体、S1 P受体1和CCR 6依赖的方式触发第2组先天淋巴细胞介导的炎症，导致HF的热性细胞死亡和不可逆的脱发。双链RNA诱导的消融模型表明，ADAM 10-Notch信号传导轴通过促进I型干扰素应答下游的β-防御素-6表达来支持上皮先天免疫。因此，ADAM 10-Notch信号传导轴介导的宿主-微生物共生的调节至关重要地保护HF免受炎症破坏，这对在慢性炎症期间维持组织完整性的策略具有影响。宿主与体内微生物的共生关系必须在体内平衡和炎症过程中维持。Sakamoto等人表明，在I型干扰素响应性上毛囊中，由ADAM 10-Notch信号支持的先天上皮屏障对于调节毛囊微生物组至关重要，其抑制导致β-防御素-6的下调，先天淋巴细胞介导的毛囊的生态失调和炎性破坏。
Hair follicles (HF) function as hubs for stem cells, immune cells, and commensal microbes, which must be tightly regulated during homeostasis and transient inflammation. Here, we found that transmembrane endopeptidase ADAM10 expression in upper HFs was crucial for regulating skin microbiota and protecting HFs and their stem cell niche from inflammatory destruction. Ablation of the ADAM10-Notch signaling axis impaired innate epithelial barrier and enabled Corynebacterium species to predominate the microbiome. Dysbiosis triggered group 2 innate lymphoid cells-mediated inflammation in an IL-7 receptor-, S1P receptor 1- and CCR6-dependent manner, leading to pyroptotic cell death of HFs and irreversible alopecia. Double-stranded RNA-induced ablation models indicated that ADAM10-Notch signaling axis bolsters epithelial innate immunity by promoting β-defensin-6 expression downstream of type I interferon responses. Thus, ADAM10-Notch signaling axis-mediated regulation of host-microbial symbiosis crucially protects HFs from inflammatory destruction, which has implications for strategies to sustain tissue integrity during chronic inflammation. Host symbiosis with commensal microorganisms must be maintained during homeostasis and inflammation. Sakamoto et al show that the innate epithelial barrier bolstered by ADAM10-Notch signaling in type I interferon-responsive upper hair follicles was crucial for regulating the follicular microbiome, inhibition of which led to downregulation of β-defensin-6, dysbiosis and inflammatory destruction of the hair follicles mediated by innate lymphoid cells.
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影响因子：
82.9
作者：
Adachi T;Kobayashi T;Sugihara E;Yamada T;Ikuta K;Pittaluga S;Saya H;Amagai M;Nagao K
通讯作者：
Nagao K
DOI：
10.3390/pathogens2010177
发表时间：
2013-03-19
期刊：
Pathogens (Basel, Switzerland)
影响因子：
--
作者：
Cobo ER;Chadee K
通讯作者：
Chadee K
影响因子：
4.8
作者：
Harder, J;Bartels, J;Schröder, JM
通讯作者：
Schröder, JM
影响因子：
4.4
作者：
Han, H;Tanigaki, K;Honjo, T
通讯作者：
Honjo, T
影响因子：
10.6
作者：
Edwards DR;Handsley MM;Pennington CJ
通讯作者：
Pennington CJ