Sepsis Is a Syndrome with Hyperactivity of TH17 Immunity with Treg Cell Over-Presentation

Background: Currently, there are two major theories for the pathogenesis of sepsis: hyperimmune and hypoimmune. Hyperimmune theory suggests that cytokine storm causes the symptoms of sepsis. On the contrary, hypoimmune theory suggests that immunosuppression causes the manifestations of sepsis. Methods: By using microarray study on peripheral leukocytes from septic patients, this study implies that hyperactivity of TH17 immunity are noted in sepsis patients. Results: I find out that innate immunity related genes are significantly up-regulated including CD14, TLR1,2,4,5,8, HSP70, CEBP proteins, AP1(JUNB, FOSL2), TGF-β, IL-6, TGF-α, CSF2 receptor, TNFRSF1A, S100A binding proteins, CCR2, formyl peptide receptor2, amyloid proteins, pentraxin, defensins, CLEC5A, whole complement machinery, CPD, NCF, MMP, neutrophil elastase, caspases, IgG and IgA Fc receptors(CD64, CD32), ALOX5, PTGS, LTB4R, LTA4H, and ICAM1. Majority of adaptive immunity genes are down-regulated including MHC related genes, TCR genes, granzymes/perforin, CD40, CD8, CD3, TCR signaling, BCR signaling, T & B cell specific transcription factors, NK killer receptors, and TH17 helper specific transcription factors(STAT3, RORA, REL). In addition, Treg related genes are up-regulated including TGFβ, IL-15, STAT5B, SMAD2/4, CD36, and thrombospondin. Conclusions: Thus, Th17 with Treg over-presentation plays important roles in the pathophysiology of sepsis.