Intracellular thiol redox status of macrophages directs the Th1 skewing in thioredoxin transgenic mice during aging

Abstract

We have been proposing the functional distinction of two classes of macrophages (Mp), namely the reductive macrophages (RMp) with high intracellular content of glutathione (GSH) and the oxidative macrophages (OMp) with reduced content. At the same time we have been investigating the variation of RMp/OMp balance during aging of mice, especially in relation to the age related onset of autoimmune diseases. In this paper we have investigated the Th1/Th2 balance of thioredoxin (TRX) transgenic (Tg) mice, with prolonged life longevity, during aging in the context of the intracellular redox status of Mp, which has been hypothesized to be crucial in regulating the Th1/Th2 balance. It was confirmed that peritoneal resident Mp of Tg mice showed the higher GSH/GSSG ratios compared with that of age matched wild type (WT) mice. The predominance of RMp was associated with the sustained maintenance of Th1 prevalence during aging until 2 years in Tg mice, whereas WT littermates showed rapid polarization to Th2 around the age of 8 months. The Tg mice showed elevation of IFN-γ and reduction of IL-10 with moderate change of IL-4 produced by CD4+ T cells. The WT mice showed inverse changes of IFN-γ/IL-4 and IFN-γ/IL-10 ratios during aging. In addition, IL-10 production by Mp was dramatically reduced in aged Tg mice. Thus, TRX Tg mice may be useful to investigate the contribution of the anti-oxidant defense mechanism during aging accompanied with increasing oxidative stress.