Homeostatic NF-κB Signaling in Steady-State Migratory Dendritic Cells Regulates Immune Homeostasis and Tolerance
Homeostatic NF-κB Signaling in Steady-State Migratory Dendritic Cells Regulates Immune Homeostasis and Tolerance
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DOI：
10.1016/j.immuni.2015.03.003
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发表时间：
2015-04-21
期刊：
影响因子：
32.4
通讯作者：
Lawrence, Toby
中科院分区：
文献类型：
--
作者：
Baratin, Myriam;Foray, Chloe;Lawrence, Toby
迁移性非淋巴组织树突状细胞 (NLT-DC) 将抗原转运至淋巴结 (LN)，是炎症环境下保护性免疫反应所必需的，并促进稳态时对自身抗原的耐受性。然而，引起稳态 NLT-DC 成熟和迁移的分子机制尚不清楚。通过比较皮肤中 NLT-DC 的转录组与引流 LN 中迁移对应物的转录组，我们发现了一种针对迁移 DC 的新型 NF-κ B 调节基因网络。我们发现，在 DC 中靶向删除 IKK beta（NF-κ B 的主要激活剂）可防止 NLT-DC 在 LN 中积累，并损害体内调节性 T 细胞转化。这与耐受性和自身免疫受损有关。 NF-kappa B 通常被认为是典型的促炎转录因子，但这项研究描述了 NF-kappa B 信号在 DC 中对于免疫稳态和耐受性的作用，这可能对自身免疫性疾病和免疫产生影响。
Migratory non-lymphoid tissue dendritic cells (NLT-DCs) transport antigens to lymph nodes (LNs) and are required for protective immune responses in the context of inflammation and to promote tolerance to self-antigens in steady-state. However, the molecular mechanisms that elicit steady-state NLT-DC maturation and migration are unknown. By comparing the transcriptome of NLT-DCs in the skin with their migratory counterparts in draining LNs, we have identified a novel NF-kappa B-regulated gene network specific to migratory DCs. We show that targeted deletion of IKK beta in DCs, a major activator of NF-kappa B, prevents NLT-DC accumulation in LNs and compromises regulatory T cell conversion in vivo. This was associated with impaired tolerance and autoimmunity. NF-kappa B is generally considered the prototypical pro-inflammatory transcription factor, but this study describes a role for NF-kappa B signaling in DCs for immune homeostasis and tolerance that could have implications in autoimmune diseases and immunity.