Microarray Analysis Reveals Sepsis Is a Syndrome with Hyperactivity of TH17 Immunity, with Over-Presentation of the Treg Cell Cytokine TGF-β.

Currently, there are two major theories regarding the pathogenesis of sepsis: hyperimmune and hypoimmune. The hyperimmune theory suggests that a cytokine storm causes the symptoms of sepsis. On the contrary, the hypoimmune theory suggests that immunosuppression causes the manifestations of sepsis. By conducting a microarray analysis on peripheral leukocytes from patients with sepsis, this study found that hyperactivity of TH17 immunity was noted in sepsis patients. Innate immunity-related genes are significantly upregulated, including , ,,,,, , proteins, AP1 ( and ), , , , receptor, , S100A binding proteins, , , amyloid proteins, pentraxin, defensins, CLEC5A, whole complement machinery, , , , neutrophil elastase, caspases, IgG and IgA Fc receptors (, ), , , , , and . The majority of adaptive immunity genes were downregulated, including MHC-related genes, TCR genes, granzymes/perforin, , , , TCR signaling, BCR signaling, T and B cell-specific transcription factors, NK killer receptors, and TH17 helper-specific transcription factors (, , and ), as well as Treg-related genes, including , , , , , and thrombospondin. The findings of this study show that Th17 with Treg over-presentation play an important role in the pathophysiology of sepsis.