Year: 2026
Type: article
Abstract: OBJECTIVE: This study aimed to investigate the therapeutic potential of sovleplenib, a selective SYK inhibitor, in aplastic anemia (AA), focusing on its effects on immune modulation and the cGAS-STING-NF-κB inflammatory axis. METHODS: An immune-mediated AA mouse model was established and treated with sovleplenib. Hematopoietic function was assessed via peripheral blood counts and bone marrow mononuclear cell (BMNC) counts. Immune cell profiles were analyzed by flow cytometry. Cytokine levels were measured by ELISA. Underlying mechanisms were explored through proteomics and Western blotting. RESULTS: T-cell ratio and decreasing the M1/M2 macrophage ratio, promoting an M2 phenotype. Concurrently, it elevated Arg-1 level while suppressing ROS, TNF-α, and IFN-β. Mechanistically, sovleplenib inhibited the activation of key pathway components (cGAS, STING, p-TBK1, p-p65). DISCUSSION: The results demonstrate sovleplenib's dual role in promoting hematopoiesis and immunomodulation. Its efficacy is mechanistically linked to the suppression of the overactivated cGAS-STING-NF-κB pathway, a key driver of inflammation in AA. CONCLUSION: Sovleplenib represents a promising targeted therapy for AA.
Source: Hematology
Authors: Tianzi Sheng, Wei Sun, Shan Xin, Chengcheng Zhou, Hong Liu
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,557
OpenAlex ID: W7127343289