Epidermal Notch1 recruits RORγ(+) group 3 innate lymphoid cells to orchestrate normal skin repair.
Epidermal Notch1 recruits RORγ(+) group 3 innate lymphoid cells to orchestrate normal skin repair.
复制标题
DOI：
10.1038/ncomms11394
复制
发表时间：
2016-04-21
影响因子：
16.6
通讯作者：
Ambler CA
中科院分区：
文献类型：
--
作者：
Li Z;Hodgkinson T;Gothard EJ;Boroumand S;Lamb R;Cummins I;Narang P;Sawtell A;Coles J;Leonov G;Reboldi A;Buckley CD;Cupedo T;Siebel C;Bayat A;Coles MC;Ambler CA
Notch在控制胚胎和成人表皮和免疫系统中的细胞命运决定方面具有明确的作用，但新出现的证据表明Notch还指导成人组织中的非细胞自主信号传导。在这里，我们表明Notch 1作为损伤响应信号发挥作用。表皮Notch诱导包括RORγ+ ILC 3的免疫细胞亚群募集到受伤的真皮中; RORγ+ ILC 3是伤口中IL 17 F的有效来源，并控制免疫和表皮细胞应答。RORγ+ ILC 3缺陷的小鼠伤口愈合不良，这是由CCL 3依赖性过程中延迟的表皮增殖和巨噬细胞募集引起的。Notch 1上调TNFα和ILC 3募集趋化因子CCL 20和CXCL 13。TNFα作为Notch 1效应子，指导ILC 3定位和伤口愈合速率。总之，这些发现表明Notch是皮肤上皮中驱动先天免疫细胞募集和正常皮肤组织修复的关键应激/损伤信号。 在正常皮肤中，Notch指导角质形成细胞终末分化。在这里，作者表明Notch 1在皮肤修复中具有更广泛的作用; Notch 1在损伤后的角质形成细胞中被激活，并驱动TNFα和炎性趋化因子的转录，从而招募ILC 3和巨噬细胞促进修复。
Notch has a well-defined role in controlling cell fate decisions in the embryo and the adult epidermis and immune systems, yet emerging evidence suggests Notch also directs non-cell-autonomous signalling in adult tissues. Here, we show that Notch1 works as a damage response signal. Epidermal Notch induces recruitment of immune cell subsets including RORγ+ ILC3s into wounded dermis; RORγ+ ILC3s are potent sources of IL17F in wounds and control immunological and epidermal cell responses. Mice deficient for RORγ+ ILC3s heal wounds poorly resulting from delayed epidermal proliferation and macrophage recruitment in a CCL3-dependent process. Notch1 upregulates TNFα and the ILC3 recruitment chemokines CCL20 and CXCL13. TNFα, as a Notch1 effector, directs ILC3 localization and rates of wound healing. Altogether these findings suggest that Notch is a key stress/injury signal in skin epithelium driving innate immune cell recruitment and normal skin tissue repair. In normal skin, Notch directs keratinocytes to terminally differentiate. Here the authors show that Notch1 has a wider role in skin repair; Notch1 is activated in keratinocytes after damage and drives transcription of TNFα and inflammatory chemokines, which in turn recruit ILC3s and macrophages that promote repair.