Sequential conversion of the redox status of macrophages dictates the pathological progression of autoimmune diabetes

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Abstract
The redox status of macrophages (Mϕ), indexed by intracellular content of glutathione (icGSH), varies sequentially along with disease progression in nonobese diabetic mice. At the stage ofearly insulitis, Mϕ skew to oxidative Mϕ (OMϕ) with decreased icGSH, then to reductive Mϕ (RMϕ) with elevated icGSH and to OMϕ after the occurrence of diabetes. RMϕ or OMϕ inducing agents either delayed or accelerated the onset of diabetes in a mutually inverse manner. RMϕ or OMϕ adoptively transferred exacerbated or ameliorated the disease progression depending on the redox status of Mϕ of recipient mice. The new paradigm that the sequential conversion of redox status of Mϕ dictates the pathological progression may provide a new insight on the mechanism underlying autoimmune diabetes.