A Wave of Regulatory T Cells into Neonatal Skin Mediates Tolerance to Commensal Microbes.
A Wave of Regulatory T Cells into Neonatal Skin Mediates Tolerance to Commensal Microbes.
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DOI：
10.1016/j.immuni.2015.10.016
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发表时间：
2015-11-17
期刊：
影响因子：
32.4
通讯作者：
Rosenblum MD
中科院分区：
文献类型：
--
作者：
Scharschmidt TC;Vasquez KS;Truong HA;Gearty SV;Pauli ML;Nosbaum A;Gratz IK;Otto M;Moon JJ;Liese J;Abbas AK;Fischbach MA;Rosenblum MD
皮肤是免疫系统和肠道细菌之间不断对话的场所。然而，使我们能够耐受皮肤溃疡而不引起破坏性炎症的分子机制尚不清楚。使用模型系统研究对S.表皮，我们证明了在新生儿生命的确定时期内的皮肤定植是建立对肠道微生物的免疫耐受所必需的。这一关键窗口的特征是高度活化的调节性T细胞（Treg）突然涌入新生儿皮肤。选择性抑制这种Treg细胞波完全消除了耐受性。因此，皮肤中的宿主-宿主关系依赖于独特的Treg细胞群，其在限定的发育窗口期间介导对细菌抗原的耐受性。这表明，新生儿生活中的皮肤微生物组组成在形成对细菌的适应性免疫反应方面至关重要，破坏这些相互作用可能会对健康产生持久的影响。
The skin is a site of constant dialogue between the immune system and commensal bacteria. However, the molecular mechanisms that allow us to tolerate the presence of skin commensals without eliciting destructive inflammation are unknown. Using a model system to study the antigen-specific response to S. epidermidis, we demonstrated that skin colonization during a defined period of neonatal life was required to establish immune tolerance to commensal microbes. This crucial window was characterized by an abrupt influx of highly activated regulatory T (Treg) cells into neonatal skin. Selective inhibition of this Treg cell wave completely abrogated tolerance. Thus, the host-commensal relationship in the skin relied on a unique Treg cell population that mediated tolerance to bacterial antigens during a defined developmental window. This suggests that the cutaneous microbiome composition in neonatal life is crucial in shaping adaptive immune responses to commensals, and disrupting these interactions may have enduring health implications.