Recombinant Protein UBC13 Improves Tissue Injury of MRL/Lpr Mice by Alleviating Th1/Th2 Immune Imbalance

This study aimed to investigate the role of T-cell imbalance in the pathogenesis of systemic lupus erythematosus (SLE), the role of Ubiquitin-binding enzyme 2N (UBC13) in the treatment of SLE.

Mice in the model group were intraperitoneally injected with normal saline. The UBC13 group was administered UBC13 recombinant protein, and the dexamethasone (DXM) group was treated with DXM for 8 weeks. Serum anti-dsDNA and ANA levels were quantified via ELISA. Histopathological changes were analyzed using H&E staining. Splenic mRNA expression of inflammatory cytokines and transcription factors was analyzed using qRT-PCR. Flow cytometry was used characterize Th1, Th2 and Treg cells populations, while western blotting was used to detect STAT3 and NF-κB signalling pathway-related proteins in thymic lysates.

UBC13 administration ameliorated splenic hyperplasia and attenuated tissue damage in MRL/lpr mice, accompanied by a reduction in serum anti-dsDNA and ANA titers. Proinflammatory cytokine production, was suppressed following UBC13 intervention. Concurrently, UBC13 restored Th1/Th2 cell equilibrium and enhanced Treg cell suppressive function. Mechanistically, UBC13 inhibited NF-κB pathway activation and suppressed STAT3 phosphorylation.

UBC13 restores the homeostasis and function of Th1/Th2 and Treg cell through suppression of STAT3 and the NF-κB signaling pathway activation, thereby mitigating SLE-induced organ damage.