Skin autonomous antibody production regulates host-microbiota interactions. Skin autonomous antibody production regulates host-microbiota interactions

Host symbiosis with its microbiota can represent a liability for the host. Indeed, while these communities of microbes broadly control host physiology, the microbiota can also promote inflammation and represent a source of local and systemic infection. The unique strategies employed by each tissue to maintain and control coexistence with commensal microbes remain largely unclear. Here we uncover that, within the skin, host protection from its microbiota depends on the remarkable ability of the skin to act as an autonomous lymphoid organ. Notably, an encounter with a new skin microbe is associated with two parallel responses both, under the control of Langerhans cells. On one hand, skin commensal promotes the development of classical germinal centers within secondary lymphoid organs leading to IgG1 and IgG3 responses. On the other hand, microbial colonization also leads to the development of tertiary lymphoid organs that can locally sustain and mature IgG2b and IgG2c responses. The ability of the skin to develop as a lymphoid compartment is at least in part mediated by the ability of the local Treg pool to convert into T follicular helper cells accumulating within organized tertiary lymphoid organs surrounding the hair follicles. Remarkably, skin autonomous production of antibodies is sufficient to control both microbial colonization within the skin as well as subsequent infection with the same commensal. Collectively these results reveal a profound compartmentalization of humoral responses between the lymph nodes and the skin. Further, this work uncovers a previously unappreciated function for the skin as a compartment able to develop, in the absence of inflammation, powerful and long-lived antibody responses independently of secondary lymphoid organs. Overall design: T cells were extracted for single cell RNA-seq from skin of mice treated with Stapholococcus epidermidies

宿主与其微生物群的共生关系可能会给宿主带来负担。实际上，尽管这些微生物群落广泛调控宿主生理功能，但微生物群也可能诱发炎症，并成为局部和全身性感染的源头。各组织维持与共生微生物共存并对其进行调控的独特机制在很大程度上仍未阐明。在此我们揭示，在皮肤中，宿主抵御其微生物群的能力依赖于皮肤作为自主淋巴器官的卓越功能。值得注意的是，接触新型皮肤微生物会触发两种平行的免疫应答，这两种应答均受朗格汉斯细胞（Langerhans cells）调控。一方面，皮肤共生微生物可促进次级淋巴器官内经典生发中心的发育，进而引发IgG1和IgG3型抗体应答。另一方面，微生物定植还会诱导三级淋巴器官的形成，后者可在局部维持并促进IgG2b与IgG2c型抗体应答的成熟。皮肤发育为淋巴隔室的能力，在一定程度上由局部调节性T细胞（Treg）池转化为滤泡辅助性T细胞（T follicular helper cells）的能力所介导，这些滤泡辅助性T细胞会聚集在毛囊周围的有序三级淋巴器官中。值得注意的是，皮肤自主产生的抗体足以同时控制皮肤内的微生物定植以及后续由同类共生微生物引发的感染。综上，这些研究结果揭示了淋巴结与皮肤之间体液免疫应答的显著区域化特征。此外，本研究还发现了此前未被认知的皮肤功能：在无炎症的情况下，皮肤可作为独立隔室，不依赖次级淋巴器官而产生强效且持久的抗体应答。总体实验设计：从经表皮葡萄球菌（Staphylococcus epidermidis）处理的小鼠皮肤中提取T细胞，进行单细胞RNA测序（single cell RNA-seq）。