EGR1 Mediated Reduction of Fibroblast Secreted-TGF-β1 Exacerbated CD8+ T Cell Inflammation and Migration in Vitiligo.
EGR1 Mediated Reduction of Fibroblast Secreted-TGF-β1 Exacerbated CD8+ T Cell Inflammation and Migration in Vitiligo.
复制标题
DOI：
10.1007/s10753-023-01922-2
复制
发表时间：
2023-10
期刊：
影响因子：
5.1
通讯作者：
Rong Jin;Hao Xu;Miao-ni Zhou;F. Lin;Wen Xu;Aie Xu
中科院分区：
文献类型：
--
作者：
Rong Jin;Hao Xu;Miao-ni Zhou;F. Lin;Wen Xu;Aie Xu
白癜风是一种T细胞介导的色素脱失性皮肤病，由黑素细胞功能障碍、环境刺激和免疫信号失调之间的复杂相互作用引起。转化生长因子-β1（TGF-β1）通常来源于调节性T细胞，长期以来在白癜风患者的外周系统中被鉴定为低水平。在这里，通过RNA测序和转录因子富集，我们发现，在响应CD 8 +T细胞分泌的干扰素-γ（IFN-γ），基质成纤维细胞下调早期生长反应1（EGFR 1）的活性，导致TGF-β1缺陷。免疫调节环缺陷进一步加剧了白癜风局部CD 8 +T细胞炎症，并促进了炎症细胞迁移。因此，成纤维细胞来源的TGF-β1在白癜风发病机制中起着重要的基质信号作用。
Vitiligo is a T cell-mediated depigment skin disease caused by the complex interplay between melanocyte dysfunction, environmental stimulation, and dysregulated immune signals. Transforming growth factor-β1 (TGF-β1), which typically derives from regulatory T cells, has long been identified at low levels in the peripheral system of vitiligo patients. Here, through RNA-sequencing and transcription factor enrichment, we revealed that in response to CD8+T cell-secreted interferon-gamma (IFN-γ), stromal fibroblast downregulates early growth response 1 (EGR1) activity, leading to TGF-β1 deficiency. The defective immune regulation loop further exacerbated local CD8+T cell inflammation and promoted inflammatory cell migration in vitiligo. Thus, fibroblast-derived TGF-β1 plays an important stromal signal in vitiligo pathogenesis.