共生微生物与毛囊形态发生协同驱动调节性T细胞迁移至新生儿皮肤。
Commensal Microbes and Hair Follicle Morphogenesis Coordinately Drive Treg Migration into Neonatal Skin.
作者信息
Scharschmidt Tiffany C, Vasquez Kimberly S, Pauli Mariela L, Leitner Elizabeth G, Chu Kevin, Truong Hong-An, Lowe Margaret M, Sanchez Rodriguez Robert, Ali Niwa, Laszik Zoltan G, Sonnenburg Justin L, Millar Sarah E, Rosenblum Michael D
机构信息
Department of Dermatology, University of California, San Francisco, San Francisco, CA, 94143, USA.
Immuno-Oncology Group, Bristol-Meyers Squibb, Redwood City, CA, 94063, USA.
出版信息
Cell Host Microbe. 2017 Apr 12;21(4):467-477.e5. doi: 10.1016/j.chom.2017.03.001. Epub 2017 Mar 23.
Regulatory T cells (Tregs) are required to establish immune tolerance to commensal microbes. Tregs accumulate abruptly in the skin during a defined window of postnatal tissue development. However, the mechanisms mediating Treg migration to neonatal skin are unknown. Here we show that hair follicle (HF) development facilitates the accumulation of Tregs in neonatal skin and that upon skin entry these cells localize to HFs, a primary reservoir for skin commensals. Further, germ-free neonates had reduced skin Tregs indicating that commensal microbes augment Treg accumulation. We identified Ccl20 as a HF-derived, microbiota-dependent chemokine and found its receptor, Ccr6, to be preferentially expressed by Tregs in neonatal skin. The Ccl20-Ccr6 pathway mediated Treg migration in vitro and in vivo. Thus, HF morphogenesis, commensal microbe colonization, and local chemokine production work in concert to recruit Tregs into neonatal skin, thereby establishing this tissue Treg niche early in life.
调节性T细胞（Tregs）对于建立对共生微生物的免疫耐受是必需的。在出生后组织发育的特定窗口期，Tregs会在皮肤中突然聚集。然而，介导Tregs迁移至新生皮肤的机制尚不清楚。在此，我们表明毛囊（HF）发育促进了Tregs在新生皮肤中的聚集，并且这些细胞进入皮肤后会定位于HF，而HF是皮肤共生菌的主要储存库。此外，无菌新生小鼠的皮肤Tregs减少，表明共生微生物增强了Tregs的聚集。我们鉴定出Ccl20是一种源自HF、依赖微生物群的趋化因子，并发现其受体Ccr6在新生皮肤的Tregs中优先表达。Ccl20-Ccr6途径在体外和体内介导了Tregs的迁移。因此，HF形态发生、共生微生物定植和局部趋化因子产生协同作用，将Tregs招募到新生皮肤中，从而在生命早期建立这种组织Treg生态位。
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