Maresin1 ameliorates acute lung injury induced by sepsis through regulating Th17/Treg balance

Xia, Haifa; Wang, Fuquan; Wang, Min; Wang, Jingxu; Sun, Shujun; Chen, Ming; Huang, Shiqian; Chen, Xiangdong; Yao, Shanglong

doi:10.1016/j.lfs.2020.117773

Cited by 36 publications

(32 citation statements)

References 37 publications

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“…However, the modulatory role of JKAP on Th1 and Th17 cell functions should be assessed by more animal or cell experiments. (2) As for the elevation of Th1 and Th17 proportions and their correlations with more severe disease in sepsis patients, it is reasonable because Th1 and Th17 cells play a role that promotes the disease progression in sepsis as reported by the previous studies [ 21 , 23 – 25 ].…”

Section: Discussionmentioning

confidence: 93%

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

Peng

2020

Ir J Med Sci

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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.

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Section: Discussionmentioning

confidence: 93%

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

Peng

2020

Ir J Med Sci

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“…The balance between Th1 and Th2, which are crucial to maintain the homeostasis of immune system, is one of causes for the development and progression of ALI [ 39 ]. The balance between Treg and Th17 cells has been confirmed to be involved in ALI/ARDS [ 40 ]. Our result also indicated that ILT3, which has an ability to modulate Th cell immune responses, was significantly upregulated in cDCs.…”

Section: Resultsmentioning

confidence: 99%

Resveratrol pretreatment mitigates LPS-induced acute lung injury by regulating conventional dendritic cells’ maturation and function

Guo

Peng

et al. 2021

Open Life Sciences

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Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a severe syndrome lacking efficient therapy and resulting in high morbidity and mortality. Although resveratrol (RES), a natural phytoalexin, has been reported to protect the ALI by suppressing the inflammatory response, the detailed mechanism of how RES affected the immune system is poorly studied. Pulmonary conventional dendritic cells (cDCs) are critically involved in the pathogenesis of inflammatory lung diseases including ALI. In this study, we aimed to investigate the protective role of RES via pulmonary cDCs in lipopolysaccharide (LPS)-induced ALI mice. Murine ALI model was established by intratracheally challenging with 5 mg/kg LPS. We found that RES pretreatment could mitigate LPS-induced ALI. Additionally, proinflammatory-skewed cytokines decreased whereas anti-inflammatory-related cytokines increased in bronchoalveolar lavage fluid by RES pretreatment. Mechanistically, RES regulated pulmonary cDCs’ maturation and function, exhibiting lower level of CD80, CD86, major histocompatibility complex (MHC) II expression, and IL-10 secretion in ALI mice. Furthermore, RES modulated the balance between proinflammation and anti-inflammation of cDCs. Moreover, in vitro RES pretreatment regulated the maturation and function of bone marrow derived dendritic cells (BMDCs). Finally, the adoptive transfer of RES-pretreated BMDCs enhanced recovery of ALI. Thus, these data might further extend our understanding of a protective role of RES in regulating pulmonary cDCs against ALI.

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“…SPMs may be expected to increase FoxP3 and Treg populations in a targeted polarization (37). Recently animal models demonstrated the regulatory function of Maresin 1 on Treg/ Th17 balance through transcription factors (72,73) suggesting a role for the inflammatory milieu in which T h 17 and Treg cells work counterregulatory of each other's function. Our data are in line with findings suggesting that IL-2-mediated mechanism by Treg cells may lead to an increase of both T h 17 and Treg cells at the same time by preventing inhibition capacity of IL-2 over T h 17 cells (74).…”

Section: Discussionmentioning

confidence: 99%

Resolvin E1 Regulates Th17 Function and T Cell Activation

et al. 2021

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Resolvin E1 (RvE1) is a specialized pro-resolving lipid mediator derived from eicosapentaenoic acid and plays a critical role in resolving inflammation and tissue homeostasis. Th17 cells are a distinct group of T helper (Th) cells with tissue-destructive functions in autoimmune and chronic inflammatory diseases via the secretion of IL-17. Dendritic cell (DC)-mediated antigen presentation regulates the Th17-induced progression of inflammation and tissue destruction. In this study, we hypothesized that the RvE1 would restore homeostatic balance and inflammation by targeting the Th17 function. We designed three experiments to investigate the impact of RvE1 on different phases of Th17 response and the potential role of DCs: First CD4+ T cells were induced by IL-6/TGFβ to measure the effect of RvE1 on Th17 differentiation in an inflammatory milieu. Second, we measured the impact of RvE1 on DC-stimulated Th17 differentiation in a co-culture model. Third, we measured the effect of RvE1 on DC maturation. RvE1 blocked the CD25, CCR6 and IL-17 expression; IL-17, IL-21, IL-10, and IL-2 production, suggesting inhibition of T cell activation, Th17 stimulation and chemoattraction. RvE1 also suppressed the activation of DCs by limiting their pro-inflammatory cytokine production. Our findings collectively demonstrated that the RvE1 targeted the Th17 activation and the DC function as a potential mechanism for inflammatory resolution and acquired immune response.

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Maresin1 ameliorates acute lung injury induced by sepsis through regulating Th17/Treg balance

Cited by 36 publications

References 37 publications

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

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

Resveratrol pretreatment mitigates LPS-induced acute lung injury by regulating conventional dendritic cells’ maturation and function

Resolvin E1 Regulates Th17 Function and T Cell Activation

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