Ubiquitin released in the plasma of whole blood during storage promotes mRNA expression of Th2 cytokines and Th2-inducing transcription factors.

Many biological molecules in the stored blood were involved in transfusion-related immunomodulation. One important effect was the differentiation bias of immune cells to Th2 type. In this study, we observed the immune regulation of extracellular ubiquitin accummulated in the plasma of whole blood on the differentiation of T help cells in vitro using ELISA and quantitative fluorescence real-time PCR with the help of LPS stimulated human peripheral blood mononuclear cells. We found extracellular ubiquitin promoted Th2 cytokine IL-4 production and Th2-inducing transcription factor STAT6 expression, but inhibited Th1 cytokine IFN-γ and Th1-inducing transcription factor T-bet, at the same time, proinflammation cytokine TNF-α was also inhibited. These findings probably contribute to the potent evidence that extracellular ubiquitin plays an indispensable role in the differentiation of T help cells which is crucial to the effects of transfusion-related immunomodulation.