Abstract: Objective To investigate the therapeutic effect of graphene quantum dots (GQDs) on acute graft-versus-host disease (aGVHD) in mice and its mechanism. Methods ① GQDs intervention groupsincluded the aGVHD+GQDs group, aGVHD+PBS group and BMT group, 10 mice in each group. The survival period and clinical symptoms, and the liver, skin and intestinal histopathological changes of mice in each group were observed. ELISA method was done for the changes of TNF-α, IL-1β, IL-10 and TGF-β cytokines in the spleen tissue, immunofluorescence staining of F4/80, iNOS, and CD206 for the infiltration of splenic macrophages and changes of M1/M2 subpopulation, and Western blot for the changes of autophagy-related proteins LC-3 and p62 in the spleen tissue. ② For 3-Methyladenine（3-MA）blocked autophagy, the mice were divided into the aGVHD+GQDs+3-MA group and aGVHD +GQDs+PBS group , 10 in each group. The survival period and clinical signs, as well as the liver, skin and intestinal histopathological changes of mice in each group were observed. Western blot was applied to detect the changes of autophagy-related proteins LC-3 and p62 in the spleen tissues. Results GQDs intervention significantly reduced the infiltration of splenic macrophages in aGVHD mice, but significantly increased the proportion of M2-type macrophages. In addition, this intervention upregulated the expression of autophagy-related protein LC3II/I in the spleen of aGVHD mice, decreased the expression of p62, activated the autophagic pathway to alleviate the symptoms of aGVHD mice, alleviated the pathological damage of target organs, and prolonged the survival. 3-MA blockade of the autophagic pathway inhibited the therapeutic effect of GQDs treatment on aGVHD mice. Conclusion GQDs could alleviate aGVHD in mice through an autophagy-dependent pathway.

Key words: Graphene quantum dots, Acute graft-versus-host disease, Macrophages, Autophagy, Signaling pathways