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

Objectives: 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.

Methods: 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.

Results: 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.

Conclusion: 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.