Figure 9. Schematics illustrating the signaling mechanisms of sleep-restriction in postoperative immunosuppression and its treatment by dexmedetomidine. Sleep-restriction exaggerates intestinal flora disorder, furtherly decreases splenic trefoil factor 2 (TFF2) expression, which subsequently leads to the increase in myeloid-derived suppressor cells (MDSCs) numbers and decrease in splenic CD8+ T cells activity. Subdiaphragmatic vagus nerve (SVN) served as an important conduit of gut microbiota-spleen communication. SR-induced exaggeration of postoperative immunosuppression was characterized by increased expression of IL-4 and IL-13 in the lung, increased M2 polarization of alveolar macrophages (AMs), decreased phagocytic activity of AMs and thus decreased antimicrobial activity in E. coli pneumonia. Dexmedetomidine treatment during SR alleviated SR-induced decrease in postoperative immunosuppression through gut microbiota and SVN.