Tofacitinib Ameliorates Murine Lupus and Its Associated Vascular Dysfunction

Area of Science:

• Immunology
• Rheumatology
• Cardiovascular Research

Background:

• Systemic lupus erythematosus (SLE) involves immune dysregulation, leading to inflammation and vascular damage.
• Current treatments for SLE do not adequately address both systemic disease and cardiovascular complications.
• Tofacitinib, a Janus kinase (JAK) inhibitor, targets cytokine signaling pathways implicated in lupus.

Purpose of the Study:

• To investigate the efficacy of tofacitinib in ameliorating lupus pathogenesis and associated vascular dysfunction in a murine model.
• To evaluate tofacitinib's impact on immune responses, disease markers, and endothelial function in lupus-prone mice.

Main Methods:

• MRL/lpr lupus-prone mice received tofacitinib or vehicle for 6-8 weeks (therapeutic and preventive arms).
• Assessed nephritis, skin inflammation, autoantibodies, cytokines, immune cell profiles, NETs release, and endothelial function.
• Compared outcomes between tofacitinib-treated and control groups.

Main Results:

• Tofacitinib significantly improved lupus nephritis, skin inflammation, and autoantibody production.
• Reduced pro-inflammatory cytokines and interferon responses; modulated NETs formation.
• Enhanced endothelium-dependent vasorelaxation and endothelial differentiation, showing efficacy in both preventive and therapeutic settings.

Conclusions:

• Tofacitinib effectively modulates innate and adaptive immune responses in murine lupus.
• The drug ameliorates lupus symptoms and improves vascular function, indicating potential for treating SLE and its cardiovascular sequelae.
• JAK inhibitors represent a promising therapeutic strategy for SLE-associated vascular damage.