Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Am J Physiol Cell Physiol. 2023 Feb 1;324(2):C395-C406. doi: 10.1152/ajpcell.00323.2022. Epub 2022 Nov 21.
Acute graft-versus-host disease (aGVHD) is a severe T cell-mediated immune response after allogeneic hematopoietic stem cell transplantation (allo-HSCT), the molecular mechanisms remain to be elucidated and novel treatments are necessary to be developed. In the present study, we found that the expression of long noncoding RNA (lncRNA) LINC01882 decreased significantly in the peripheral blood CD4 T lymphocytes of patients with aGVHD than non-aGVHD patients. In addition, lncRNA LINC01882 overexpression promoted Treg differentiation but exhibited no effects on Th17 percentages, while its knockdown resulted in opposite effects. Mechanistically, lncRNA LINC01882 could competitively bind with let-7b-5p to prevent the degradation of its target gene smad2, which acts as a promoter in Treg differentiation. Furthermore, the mice cotransplanted with LINC01882-overexpressed CD4 T cells with PBMCs had a lower histological GVHD score and higher survival rate compared with control mice. In conclusion, our study discloses a novel LINC01882/let-7b-5p/smad2 pathway in the modulation of aGVHD and indicates that lncRNA LINC01882 could be a promising biomarker and therapeutic target for patients with aGVHD.
急性移植物抗宿主病（aGVHD）是异基因造血干细胞移植（allo-HSCT）后一种严重的 T 细胞介导的免疫反应，其分子机制尚待阐明，需要开发新的治疗方法。在本研究中，我们发现 aGVHD 患者外周血 CD4 T 淋巴细胞中的长非编码 RNA（lncRNA）LINC01882 表达明显降低。此外，lncRNA LINC01882 的过表达促进了 Treg 分化，但对 Th17 百分比没有影响，而其敲低则产生相反的效果。机制上，lncRNA LINC01882 可以与 let-7b-5p 竞争性结合，防止其靶基因 smad2 的降解，而 smad2 在 Treg 分化中起促进作用。此外，与对照组小鼠相比，共转染 LINC01882 过表达 CD4 T 细胞和 PBMCs 的小鼠的组织学 GVHD 评分更低，存活率更高。总之，我们的研究揭示了一个新的 LINC01882/let-7b-5p/smad2 通路在调节 aGVHD 中的作用，并表明 lncRNA LINC01882 可能成为 aGVHD 患者有前途的生物标志物和治疗靶点。
