research assistant professor University of Florida, United States
Introduction/Rationale: mTOR signaling is overactive in systemic lupus erythematosus (SLE) and plays a key role in the disease pathogenesis by disrupting the function of immune cells. Among them, mTOR altered macrophage function through helping polarize anti-inflammatory M2 macrophage. Rapamycin (an mTOR inhibitor) can induce a shift toward the pro-inflammatory M1 macrophage. Pristane ( a hydrocarbon) induces a lupus-like autoimmune syndrome, and it induces serious life-threatening lung Diffuse Alveolar Hemorrhage (DAH) in C57BL/6 mice, but not in Balb/c mice. M1 macrophage are central to the pathogenesis of DAH, contributing to the ongoing inflammation and damage in the lung tissue. mTOR pathway overactivation contributes to inflammation and autoimmunity, making it a promising therapeutic target in SLE.
Methods: flow cytoemtry and real time PCR
Results: We found rapamycin can induce DAH development in 60% of pristane treated Balb/c mice and aggravate DAH development in C57BL/6 mice from 60% to 80%. Circulating CD138+ proinflammatory monocytes significantly increased in Rapamycin treated pristane mice. Further study found that mTOR activity is higher in pristane treated Balb/c mice than C57BL/6 mice and pristane could increase mTOR activity in RAW cells in vitro .
Conclusion: These findings indicate the activity of mTOR, the central regulator of metabolic reprogramming, in myeloid cells influences the clinical phenotype of SLE.
