课题组人员报道转录因子Etv3在成熟的DCs中优先表达，包括组织源性迁移DCs (migDCs)，并促进其稳态成熟和CCR7依赖性迁移。Etv3整体缺失或DC特异性缺失小鼠表现为CD25低调节性T （Treg）细胞扩增、常规T细胞自发活化和多器官T细胞浸润。Etv3缺乏加剧了TLR7驱动的系统性红斑狼疮（SLE）样疾病，支持了人类Etv3与SLE遗传关联的报道。Etv3缺陷的migDCs上调了多种共刺激分子，包括OX40配体（OX40L/TNFSF4），其阻断部分挽救了Treg细胞异常。这些结果表明，Etv3是DC耐受原功能的重要调节因子，并与人类自身免疫的调节有关。
据介绍，树突状细胞（DC）促进免疫耐受维持在稳定状态。
附：英文原文
Title: Transcription factor Etv3 controls the tolerogenic function of dendritic cells
Author: Nicholas M. Adams, Daniel Martinez-Krams, Eduardo Esteva, Ai C. Ra, Allegra Iliadi Alexiou, Hua Jin, Tae Jin Yun, Rayan Sleiman Tellaoui, Tenny Mudianto, Emily Vollmer, Ekaterina Novikova, Yanjun Tan, William Huntley, Oleg Krichevsky, Igor Dolgalev, Peter Izmirly, Jill P. Buyon, Andre L. Moreira, Amanda W. Lund, Boris Reizis
Issue&Volume: 2026-02-12
Abstract: Dendritic cells (DCs) facilitate the maintenance of immunological tolerance in the steady state. We report that transcription factor Etv3 is preferentially expressed in mature DCs, including tissue-derived migratory DCs (migDCs), and facilitates their homeostatic maturation and CCR7-dependent migration. Mice with global or DC-specific deletion of Etv3 manifested the expansion of CD25low regulatory T (Treg) cells, spontaneous activation of conventional T cells, and multiorgan T cell infiltration. Etv3 deficiency exacerbated TLR7-driven systemic lupus erythematosus (SLE)–like disease, supporting the reported genetic association of human ETV3 with SLE. Etv3-deficient migDCs up-regulated multiple costimulatory molecules, including OX40 ligand (OX40L/TNFSF4), whose blockade partially rescued the Treg cell abnormalities. These results identify Etv3 as an essential regulator of the tolerogenic function of DCs and implicate it in the regulation of human autoimmunity.
DOI: ads1246
Source: https://www.science.org/doi/10.1126/science.ads1246