🧫 Experiment Protocol
ValidationInflammatory bowel diseaseNAMPTRag1-/- mice with DSS-induced colitisproposed
Mechanistic validation experiment using Rag1-/- mice (lacking mature T and B cells) to determine whether FK866's therapeutic effects are primarily mediated through innate immune cells rather than adaptive immunity. This experiment was crucial for establishing that FK866's anti-inflammatory effects are independent of T and B cell responses and are primarily mediated through altered monocyte/macrophage biology. The effectiveness of FK866 in Rag1-/- mice confirmed that the therapeutic mechanism involves direct modulation of innate immune cell function, particularly macrophage polarization, rather than effects on adaptive immune responses.
PRIMARY OUTCOME
Anti-inflammatory efficacy in absence of adaptive immunity
EXPECTED OUTCOMES
Maintained anti-inflammatory efficacy demonstrating innate immune mechanism
SUCCESS CRITERIA
Significant anti-inflammatory effects in the absence of T and B cells
PROTOCOL
DSS-induced colitis in Rag1-/- mice treated with FK866, assessment of inflammatory parameters and innate immune cell responses