A Novel Human Systemic Lupus Erythematosus Model in Humanised Mice

Area of Science:

• Immunology
• Rheumatology
• Pre-clinical disease modeling

Background:

• Existing mouse models for Systemic Lupus Erythematosus (SLE) have limitations due to significant differences between human and mouse immune systems.
• There is a critical need for accurate in vivo models that recapitulate human SLE for translational research.

Purpose of the Study:

• To establish and characterize a novel SLE model utilizing a human immune system in immunodeficient mice (humanized mice).
• To assess the recapitulation of key clinical and immunological features of human SLE in this new model.

Main Methods:

• Immunodeficient mice were reconstituted with a human immune system.
• Pristane was administered to induce SLE-like pathology.
• Key immunological and clinical parameters were analyzed, including autoantibody production, organ pathology, immune cell populations, and cytokine profiles.

Main Results:

• The humanized mouse model exhibited hallmark SLE features: human anti-nuclear autoantibodies, lupus nephritis, and pulmonary serositis.
• Observed lymphopenia, systemic hyperactivation of human B and T cells, and expansion of specific memory B cell subsets.
• Elevated production of pro-inflammatory human cytokines (IFN-γ, IL-8, IL-18, MCP-1, IL-6) and type I IFN signature genes in hepatocytes were detected.

Conclusions:

• This humanized mouse model effectively recapitulates critical clinical and immunological aspects of human SLE.
• The model provides a valuable platform for investigating human-specific SLE mechanisms and evaluating novel immunotherapies.
• Advancements in humanized mouse models are crucial for facilitating translational studies in SLE.