Role of the NF-κB Family Member RelB in Regulation of Foxp3+ Regulatory T Cells In Vivo
Role of the NF-κB Family Member RelB in Regulation of Foxp3+ Regulatory T Cells In Vivo
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NF-κB 家族成员 RelB 在体内调节 Foxp3+ 调节性 T 细胞中的作用
DOI：
10.4049/jimmunol.1701310
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发表时间：
2018-02-15
影响因子：
4.4
通讯作者：
Xiao, Xiang
中科院分区：
文献类型：
--
作者：
Li, Junhui;Chen, Shuqiu;Xiao, Xiang
核因子-kB家族成员RelB是一种重要的转录因子，能够调节多种免疫和炎症反应。然而，它在体内对Foxp3(+)调节性T细胞(Tregs)的调节作用尚不清楚。在这项研究中，我们证明了Relb的胚系缺失导致了全身自身免疫，这与Foxp3(+)Tregs在淋巴和非淋巴器官中的显著积聚有关。来自RelB缺陷小鼠的Foxp3(+)Tregs在体内外具有抑制T效应细胞的功能，而来自RelB缺陷小鼠的Foxp3(+)T效应细胞表现出高度激活的特征，并自发产生高水平的IL-2。令人惊讶的是，T细胞中Relb有条件缺失的小鼠(C4CRE Relb f/f小鼠)或Foxp3(+)Tregs特异性缺失的小鼠(Foxp3(Cre)Relb(f/)f小鼠)没有显示出自身免疫的迹象，并且外周Foxp3(+)Tregs的频率与野生型C57BL/6对照组相似。两个品系的条件性基因敲除小鼠也都有一个正常的常规T细胞室。然而，用野生型C57BL/6骨髓细胞重组RAG-1 2/2 Relb 2/2宿主后，T效应细胞高度活化，Foxp3(+)T细胞显著扩增。这些数据表明，生殖系RelB缺陷小鼠的自身免疫表型很可能是由T细胞外在机制引起的，需要进一步的研究来揭示这些机制。
The NF-kB family member RelB is an important transcription factor that is capable of regulating diverse immune and inflammatory responses. However, its role in the regulation of Foxp3(+) regulatory T cells (Tregs) in vivo is poorly defined. In this study, we demonstrated that germline deletion of Relb resulted in systemic autoimmunity, which is associated with significant accumulation of Foxp3(+) Tregs in lymphoid and nonlymphoid organs. Foxp3(+) Tregs from RelB-deficient mice were functional and capable of suppressing T effector cells in vitro and in vivo, but Foxp3 2 T effector cells from RelB-deficient mice showed features of hyperactivation and spontaneously produced high levels of IL-2. Surprisingly, mice with conditional deletion of Relb in T cells (Cd4 Cre Relb f/f mice) or specifically in Foxp3(+) Tregs (Foxp3(Cre) Relb(f/)f mice) did not show signs of autoimmunity and had similar frequencies of Foxp3(+) Tregs in the periphery as wild-type C57BL/6 controls. Both strains of conditional knockout mice also had a normal conventional T cell compartment. However, reconstituting Rag-1 2/2 Relb 2/2 hosts with wild-type C57BL/6 bone marrow cells led to hyperactivation of T effector cells, as well as marked expansion of Foxp3(+) T cells. These data suggest that the autoimmune phenotype in germline RelB-deficient mice is most likely caused by T cell-extrinsic mechanisms, and further studies are warranted to uncover such mechanisms.