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. B...
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-06-01
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| Series: | Current Issues in Molecular Biology |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1467-3045/47/6/435 |
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| Summary: | 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 <i>CD14</i>, <i>TLR1</i>,<i>2</i>,<i>4</i>,<i>5</i>,<i>8</i>, <i>HSP70</i>, <i>CEBP</i> proteins, AP1 (<i>JUNB</i> and <i>FOSL2</i>), <i>TGFB1</i>, <i>IL6</i>, <i>TGFA</i>, <i>CSF2</i> receptor, <i>TNFRSF1A</i>, S100A binding proteins, <i>CCR2</i>, <i>FPR2</i>, amyloid proteins, pentraxin, defensins, CLEC5A, whole complement machinery, <i>CPD</i>, <i>NCF</i>, <i>MMP</i>, neutrophil elastase, caspases, IgG and IgA Fc receptors (<i>CD64</i>, <i>CD32</i>), <i>ALOX5</i>, <i>PTGS</i>, <i>LTB4R</i>, <i>LTA4H</i>, and <i>ICAM1</i>. The majority of adaptive immunity genes were downregulated, including MHC-related genes, TCR genes, granzymes/perforin, <i>CD40</i>, <i>CD8</i>, <i>CD3</i>, TCR signaling, BCR signaling, T and B cell-specific transcription factors, NK killer receptors, and TH17 helper-specific transcription factors (<i>STAT3</i>, <i>RORA</i>, and <i>REL</i>), as well as Treg-related genes, including <i>TGFB1</i>, <i>IL15</i>, <i>STAT5B</i>, <i>SMAD2/4</i>, <i>CD36</i>, and thrombospondin. The findings of this study show that Th17 with Treg over-presentation play an important role in the pathophysiology of sepsis. |
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| ISSN: | 1467-3037 1467-3045 |