The correlation between Jun N-terminal kinase pathway-associated phosphatase and Th1 cell or Th17 cell in sepsis and their potential roles in clinical sepsis management

Abstract

Background We aimed to investigate the association between Jun N-terminal kinase (JNK) pathway-associated phosphatase (JKAP) and T helper type 1 (Th1) cell or Th17 cell, and their clinical values in sepsis patients. Methods Totally 125 sepsis patients and 100 healthy subjects as controls were included. Peripheral blood was extracted from each sepsis patient and each control, then serum and peripheral blood mononuclear cell (PBMC) were separated. JKAP and inflammatory cytokines were detected in serum by ELISA; Th1 cell or Th17 cell proportion was detected in PBMC using flow cytometry. Results JKAP level was downregulated while Th1 and Th17 cell proportions were upregulated in sepsis patients compared with controls. JKAP level negatively correlated with Th1 cell proportion in sepsis patients and controls, while was only negatively associated with Th17 cell proportion in sepsis patients but not in controls. In sepsis patients, JKAP level negatively associated with TNF-α, IL-1β, and IL-17 expressions. Meanwhile, JKAP level negatively but Th17 cell proportion positively correlated with acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) scores; however, Th1 cell proportion only positively associated with APACHE II score but not SOFA score. Additionally, JKAP level was reduced, while Th1 and Th17 cell proportions were increased in septic deaths compared with survivors. Multivariate logistic regression model disclosed that JKAP level and Th17 cell proportion independently predicted 28-day mortality. Conclusion Blood JKAP correlates with decreased Th1 and Th17 cells, also associates with reduced inflammatory cytokines, disease severity, and favorable outcome in sepsis patients.

Th17, rather than Th1 cell proportion, is closely correlated with elevated disease severity, higher inflammation level, and worse prognosis in sepsis patients

“…A very recent study suggests that Th1 and Th17 cell proportions are associated with increased septic mortality risk 16 . In this study, it was observed that Th1 and Th17 cell proportions were both elevated in septic deaths compared with survivors.…”

“…Although it has been addressed that Th1 and Th17 cells play vital roles in the progression of sepsis, 9‐14 the proportions of Th1 and Th17 cells in patients with sepsis remain largely unclear. One previous study suggested that RAR‐related orphan receptor‐γ protein and T‐bet are both reduced in elderly sepsis patients compared with elderly patients with infection alone, indicating decreased Th1 and Th17 cell proportions in elderly septic patients, 15 while another very recent study reported that in sepsis patients, Th1 and Th17 cell proportions are elevated compared with healthy subjects 16 . However, these studies are restricted by their small sample sizes, and Th1, Th17 cell proportions in sepsis patients should be further validated with larger sample sizes.…”

“…Regarding the correlation in Th1 and Th17 cell proportions with sepsis patients’ clinical characteristics, previous studies suggested that in sepsis patients, Th1 and Th17 cell proportions are positively correlated with APACHE II score 16 . In the present study, we found that Th1 cell proportion was strongly correlated with IFN‐γ but weakly correlated with TNF‐α and IL‐17, while Th17 cell proportion showed faint correlation with IFN‐γ, but strong correlations with TNF‐α and IL‐17.…”

“…It is supposed that Th1 cells release their related cytokine interferon‐γ (IFN‐γ) to exacerbate inflammation in the lipopolysaccharide‐induced sepsis cell model, 9,10 and Th17 cells release their related cytokines interleukin‐17 (IL‐17) and tumor necrosis factor‐α (TNF‐α) to directly participate in inflammation and multiple organ injury in sepsis model cells/mice 11‐14 . Besides, previous studies also imply that Th1 and Th17 cells are dysregulated in sepsis patients, and they possess certain values in discriminating sepsis patients from healthy subjects 15,16 . However, the prognostic values of Th1 and Th17 cells in sepsis patients were largely unclear.…”

JKAP relates to disease risk, severity, and Th1 and Th17 differentiation in Parkinson's disease

“…In terms of regulation of CD4 + T cells, JKAP is reported to repress CD4 + T‐cell activation as well as its differentiation into Th1 and Th17 cells in systemic lupus erythematosus nephritis and inflammatory bowel disease 12,13 . Clinically, JKAP negatively correlates with Th17 cell secreted IL‐17 in inflammatory bowel disease patients, and negatively correlates with Th1 cells as well as Th17 cells in sepsis patients 12,23 . But to date, the relation between JKAP and CD4 + T cells in PD patients is not uncovered yet.…”