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: Yu-Ju Chen, Jang-Jih Lu, Chih-Pei Lin, Wan-Chung Hu
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Current Issues in Molecular Biology
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Online Access:https://www.mdpi.com/1467-3045/47/6/435
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author Yu-Ju Chen
Jang-Jih Lu
Chih-Pei Lin
Wan-Chung Hu
author_facet Yu-Ju Chen
Jang-Jih Lu
Chih-Pei Lin
Wan-Chung Hu
author_sort Yu-Ju Chen
collection DOAJ
description 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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spelling doaj-art-641f4cf9bbb046f5a9ef57f612119ae72025-08-20T03:27:10ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452025-06-0147643510.3390/cimb47060435Microarray Analysis Reveals Sepsis Is a Syndrome with Hyperactivity of TH17 Immunity, with Over-Presentation of the Treg Cell Cytokine TGF-βYu-Ju Chen0Jang-Jih Lu1Chih-Pei Lin2Wan-Chung Hu3Department of Laboratory Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 289 Jianguo Road, Xindian District, New Taipei City 231, TaiwanDepartment of Laboratory Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 289 Jianguo Road, Xindian District, New Taipei City 231, TaiwanDepartment of Laboratory Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 289 Jianguo Road, Xindian District, New Taipei City 231, TaiwanDepartment of Clinical Pathology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 289 Jianguo Road, Xindian District, New Taipei City 231, TaiwanCurrently, 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.https://www.mdpi.com/1467-3045/47/6/435sepsisTh17innate immunityadaptive immunityTreg
spellingShingle Yu-Ju Chen
Jang-Jih Lu
Chih-Pei Lin
Wan-Chung Hu
Microarray Analysis Reveals Sepsis Is a Syndrome with Hyperactivity of TH17 Immunity, with Over-Presentation of the Treg Cell Cytokine TGF-β
Current Issues in Molecular Biology
sepsis
Th17
innate immunity
adaptive immunity
Treg
title Microarray Analysis Reveals Sepsis Is a Syndrome with Hyperactivity of TH17 Immunity, with Over-Presentation of the Treg Cell Cytokine TGF-β
title_full Microarray Analysis Reveals Sepsis Is a Syndrome with Hyperactivity of TH17 Immunity, with Over-Presentation of the Treg Cell Cytokine TGF-β
title_fullStr Microarray Analysis Reveals Sepsis Is a Syndrome with Hyperactivity of TH17 Immunity, with Over-Presentation of the Treg Cell Cytokine TGF-β
title_full_unstemmed Microarray Analysis Reveals Sepsis Is a Syndrome with Hyperactivity of TH17 Immunity, with Over-Presentation of the Treg Cell Cytokine TGF-β
title_short Microarray Analysis Reveals Sepsis Is a Syndrome with Hyperactivity of TH17 Immunity, with Over-Presentation of the Treg Cell Cytokine TGF-β
title_sort microarray analysis reveals sepsis is a syndrome with hyperactivity of th17 immunity with over presentation of the treg cell cytokine tgf β
topic sepsis
Th17
innate immunity
adaptive immunity
Treg
url https://www.mdpi.com/1467-3045/47/6/435
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