Pan-organ damage analysis in the R848-induced systemic lupus erythematosus mouse model

Area of Science:

• Immunology
• Autoimmune Diseases
• Animal Models

Background:

• Systemic lupus erythematosus (SLE) is a complex autoimmune disease causing multi-organ dysfunction.
• Resiquimod (R848) is utilized to establish murine models of SLE.
• Limited comprehensive data exists on organ-specific involvement in R848-induced SLE models.

Purpose of the Study:

• To systematically investigate and characterize the systemic organ involvement in the R848-induced SLE mouse model.
• To elucidate the differences in organ damage and inflammatory responses within this model.

Main Methods:

• Induction of SLE in C57BL/6 mice using R848 over four weeks.
• Histopathological examination (H&E staining) of multiple organs.
• Analysis of toll-like receptors (TLRs) and inflammatory factors via RT-qPCR and Western blotting.
• Flow cytometry for T- and B-cell subset analysis.
• Immunofluorescence for detecting immune complex deposition in kidneys.

Main Results:

• R848 successfully induced an SLE-like phenotype, including splenomegaly, anti-dsDNA antibodies, and immune complex deposition.
• Significant pathological changes were observed in bone, thymus, spleen, and knee joints, with minimal impact on the heart.
• Organ-specific expression profiles of TLRs and inflammatory factors (Tnf, Ifng, Il6, Il10) were noted.
• Elevated TLR7/8 and TNF-α protein levels were predominantly found in the spleen.

Conclusions:

• R848-induced SLE mice display systemic immune dysregulation with variable organ damage.
• Inflammatory responses and TLR7/8-mediated factor expression show organ-specific patterns.
• This study provides a foundation for understanding the multisystem mechanisms underlying SLE.