Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, New York, NY 10032; and.
J Immunol. 2018 Apr 1;200(7):2362-2371. doi: 10.4049/jimmunol.1800042. Epub 2018 Feb 19.
CD4Foxp3 regulatory T cells (Tregs) are essential regulators of immune responses. Perturbation of Treg homeostasis or function can lead to uncontrolled inflammation and autoimmunity. Therefore, understanding the molecular mechanisms involved in Treg biology remains an active area of investigation. It has been shown previously that the NF-κB family of transcription factors, in particular, the canonical pathway subunits, c-Rel and p65, are crucial for the development, maintenance, and function of Tregs. However, the role of the alternative NF-κB pathway components, p100 and RelB, in Treg biology remains unclear. In this article, we show that conditional deletion of the p100 gene, , in Tregs, resulted in massive inflammation because of impaired suppressive function of -deficient Tregs. Surprisingly, mice lacking RelB in Tregs did not exhibit the same phenotype. Instead, deletion of both and rescued the inflammatory phenotype, demonstrating an essential role for p100 as an inhibitor of RelB in Tregs. Our data therefore illustrate a new role for the alternative NF-κB signaling pathway in Tregs that has implications for the understanding of molecular pathways driving tolerance and immunity.
CD4+Foxp3+ 调节性 T 细胞（Tregs）是免疫反应的重要调节者。Treg 稳态或功能的破坏可导致不受控制的炎症和自身免疫。因此，了解 Treg 生物学中涉及的分子机制仍然是一个活跃的研究领域。先前已经表明，NF-κB 转录因子家族，特别是经典途径亚基 c-Rel 和 p65，对于 Tregs 的发育、维持和功能至关重要。然而，替代 NF-κB 途径成分 p100 和 RelB 在 Treg 生物学中的作用尚不清楚。在本文中，我们表明 Tregs 中 p100 基因的条件缺失导致了大量炎症，因为 -缺陷 Tregs 的抑制功能受损。令人惊讶的是，Tregs 中缺乏 RelB 的小鼠并没有表现出相同的表型。相反，缺失 和 挽救了炎症表型，表明 p100 作为 Tregs 中 RelB 的抑制剂具有重要作用。因此，我们的数据说明了替代 NF-κB 信号通路在 Tregs 中的新作用，这对理解驱动耐受和免疫的分子途径具有重要意义。
