Long noncoding RNA LINC01882 ameliorates aGVHD via skewing CD4 ⁺ T cell differentiation toward Treg cells

Abstract

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.