Baicalin suppresses Th1 and Th17 responses and promotes Treg response to ameliorate sepsis-associated pancreatic injury via the RhoA-ROCK pathway

Li, Pingping; Zhou, Xiao; Yan, Huan; Lu, Xiulan; Zhang, Xiaopeng; Luo, Lan; Long, Caixia; Zhu, Yimin

doi:10.1016/j.intimp.2020.106685

Cited by 29 publications

(30 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Further, CCND1 has been reported to be negatively correlated with T cell activation ( Lu et al., 2019 ). ROCK was also the key regulator of T-lymphocyte development, activation, and differentiation ( Saoudi et al., 2014 ), and the RhoA-ROCK pathway is the specific pathway for Th1, Th17, and Treg responses ( Liu et al., 2020 ). This information suggests that the function of CD4 + CD8 low+ T cells may be involved in negatively regulating the activity of T cells, based on the high expression of CCND1, ROCK1, FOXO1, and FOXO3.…”

Section: Resultsmentioning

confidence: 99%

“…Meanwhile, genes involved in the “FoxO signaling pathway” and the “TGF-beta signaling pathway” were highly expressed in the CD4 + CD8 low+ (CD8 low+ ) T cell population, which implied that the function of CD4 + CD8 low+ T cells differed from CD8 + T cells. Specifically, highly expressed genes in CD4 + CD8 low+ T cells, including ROCK1 ( Liu et al., 2020 ), FOXO1 ( Ouyang et al., 2012 ), and FOXO3 ( Kerdiles et al., 2010 ), have been reported to involve in the development and function of Treg, which suggests that the function of CD4 + CD8 low+ T cells may be involved in negative regulation of T cells functions.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The Transcriptional Differences of Avian CD4+CD8+ Double-Positive T Cells and CD8+ T Cells From Peripheral Blood of ALV-J Infected Chickens Revealed by Smart-Seq2

Dai

Zhao

et al. 2021

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

It is well known that chicken CD8+ T cell response is vital to clearing viral infections. However, the differences between T cell subsets expressing CD8 receptors in chicken peripheral blood mononuclear cells (PBMCs) have not been compared. Herein, we used Smart-Seq2 scRNA-seq technology to characterize the difference of chicken CD8high+, CD8high αα+, CD8high αβ+, CD8medium+, and CD4+CD8low+ T cell subsets from PBMCs of avian leukosis virus subgroup J (ALV-J)-infected chickens. Weighted gene co-expression network analysis (WGCNA) and Trend analysis revealed that genes enriched in the “Cytokine–cytokine receptor interaction” pathway were most highly expressed in the CD8high αα+ T cell population, especially T cell activation or response-related genes including CD40LG, IL2RA, IL2RB, IL17A, IL1R1, TNFRSF25, and TNFRSF11, suggesting that CD8high αα+ T cells rather than other CD8 subpopulations were more responsive to ALV-J infections. On the other hand, genes involved in the “FoxO signaling pathway” and “TGF-beta signaling pathway” were most highly expressed in the CD4+CD8low+ (CD8low+) T cell population and the function of CD4+CD8low+ T cells may play roles in negatively regulating the functions of T cells based on the high expression of CCND1, ROCK1, FOXO1, FOXO3, TNFRSF18, and TNFRSF21. The selected gene expressions in CD8+ T cells and CD4+CD8low+ double-positive T cells confirmed by qRT-PCR matched the Smart-Seq2 data, indicating the reliability of the smart-seq results. The high expressions of Granzyme K, Granzyme A, and CCL5 indicated the positive response of CD8+ T cells. Conversely, CD4+CD8+ T cells may have the suppressor activity based on the low expression of activation molecules but high expression of T cell activity suppressor genes. These findings verified the heterogeneity and transcriptional differences of T cells expressing CD8 receptors in chicken PBMCs.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Transcriptional Differences of Avian CD4+CD8+ Double-Positive T Cells and CD8+ T Cells From Peripheral Blood of ALV-J Infected Chickens Revealed by Smart-Seq2

Dai

Zhao

et al. 2021

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

show abstract

“…), increasing the proportion and absolute number of Tregs is critical to restore immune-inflammatory homeostasis, and reduce tissue damage and organs injury. Animals depleted of Tregs at this stage are unable to resolve SIRS and die from extensive tissue damage and MODS (20,21,70,81,98,104,108,174).…”

Section: Time-dependent Treg Patterns In Sepsismentioning

confidence: 99%

“…In sepsis, reduced T cell function is associated with increased expression of Foxp3 (16)(17)(18). CD4+ T helper 17 cells (Th17) represent the pro-inflammatory subpopulation, while Tregs promote anti-inflammatory effects (19)(20)(21)(22). This review explores the current controversial, and sometimes conflicting, conclusions about Tregs in the pathophysiology of sepsis.…”

Section: Introductionmentioning

confidence: 99%

Regulatory T Cells: Angels or Demons in the Pathophysiology of Sepsis?

et al. 2022

View full text Add to dashboard Cite

Sepsis is a syndrome characterized by life-threatening organ dysfunction caused by the dysregulated host response to an infection. Sepsis, especially septic shock and multiple organ dysfunction is a medical emergency associated with high morbidity, high mortality, and prolonged after-effects. Over the past 20 years, regulatory T cells (Tregs) have been a key topic of focus in all stages of sepsis research. Tregs play a controversial role in sepsis based on their heterogeneous characteristics, complex organ/tissue-specific patterns in the host, the multi-dimensional heterogeneous syndrome of sepsis, the different types of pathogenic microbiology, and even different types of laboratory research models and clinical research methods. In the context of sepsis, Tregs may be considered both angels and demons. We propose that the symptoms and signs of sepsis can be attenuated by regulating Tregs. This review summarizes the controversial roles and Treg checkpoints in sepsis.

show abstract

“…The JAK/STAT pathway is considered as one of the major signaling pathways involved in sepsis (12) and is a part of many key cytokine signaling pathways in the pathogenesis of sepsis, such as interleukin (IL)-4, IL-6, IL-10, IL-12, and interferon (IFN)-g (13)(14)(15). In the early onset of sepsis, the body responds to infection with strong immune responses, that are manifested by the massive mobilization of pro-inflammatory cells and proinflammatory factors (16), which significantly elevates the levels of pro-inflammatory cytokines such as IL-1b and IL-6, and causes an imbalance in the helper T cell (Th) 1/Th2 and Th17/ Treg ratios (17)(18)(19). A prospective observational study found that the imbalanced ratio in the Th17/Treg was correlated with the severity and prognosis of sepsis patients (20).…”

Section: Introductionmentioning

confidence: 99%

The Study on the Regulation of Th Cells by Mesenchymal Stem Cells Through the JAK-STAT Signaling Pathway to Protect Naturally Aged Sepsis Model Rats

et al. 2022

View full text Add to dashboard Cite

Sepsis is the leading cause of death among patients, especially elderly patients, in intensive care units worldwide. In this study, we established a sepsis model using naturally aged rats and injected 5×106 umbilical cord-derived MSCs via the tail vein. Each group of rats was analyzed for survival, examined for biochemical parameters, stained for organ histology, and analyzed for the Th cell subpopulation ratio and inflammatory cytokine levels by flow cytometry. Western blotting was performed to detect the activity of the JAK-STAT signaling pathway. We designed the vitro experiments to confirm the regulatory role of MSCs, and verified the possible mechanism using JAK/STAT inhibitors. It was revealed from the experiments that the 72 h survival rate of sepsis rats treated with MSCs was significantly increased, organ damage and inflammatory infiltration were reduced, the levels of organ damage indicators were decreased, the ratios of Th1/Th2 and Th17/Treg in peripheral blood and spleen were significantly decreased, the levels of pro-inflammatory cytokines such as IL-6 were decreased, the levels of anti-inflammatory cytokines such as IL-10 were increased, and the levels of STAT1 and STAT3 phosphorylation were reduced. These results were validated in in vitro experiments. Therefore, this study confirms that MSCs can control the inflammatory response induced by sepsis by regulating Th cells and inflammatory factors, and that this leads to the reduction of tissue damage, protection of organ functions and ultimately the improvement of survival in aged sepsis model rats. Inhibition of the JAK-STAT signaling pathway was surmised that it may be an important mechanism for their action.

show abstract

Baicalin suppresses Th1 and Th17 responses and promotes Treg response to ameliorate sepsis-associated pancreatic injury via the RhoA-ROCK pathway

Cited by 29 publications

References 48 publications

The Transcriptional Differences of Avian CD4+CD8+ Double-Positive T Cells and CD8+ T Cells From Peripheral Blood of ALV-J Infected Chickens Revealed by Smart-Seq2

The Transcriptional Differences of Avian CD4+CD8+ Double-Positive T Cells and CD8+ T Cells From Peripheral Blood of ALV-J Infected Chickens Revealed by Smart-Seq2

Regulatory T Cells: Angels or Demons in the Pathophysiology of Sepsis?

The Study on the Regulation of Th Cells by Mesenchymal Stem Cells Through the JAK-STAT Signaling Pathway to Protect Naturally Aged Sepsis Model Rats

Contact Info

Product

Resources

About