Comparison of Regulatory B & T Cells and Innate Immune Responses in Children with Different Severity Sepsis and Serial Analysis of the Immunomodulatory Effects on Mice with Different Severity Sepsis Treated by Different Doses of Mesenchymal Stem Cells.

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details


Sepsis is a challenging, dynamic, pathophysiology requiring expertise in diagnosis and management. Controversy exists as to the most sensitive early indicators of sepsis and sepsis severity. To survey a serial change of proinflammatory biomarkers in innate immunity is important and useful to manage patients with sepsis and to predict clinical outcomes. Toll-like receptors (TLRs) can activate immune responses by recognizing a foreign microbe’s product. The stimulation of TLRs can trigger the activation of two downstream signaling pathways: the myeloid differentiation factor 88 (MyD88) dependent and independent pathways. In addition, regulatory B (Breg) and regulatory T (Treg) cells are more and more important because they can exert the immunosuppressive function during sepsis. Based on our prelimiting data, the expressions of TLRs signaling pathways, Treg and Breg showed different role in murine sepsis. Furthermore, mesenchymal stem cells (MSCs) have been shown to have immunosuppressive properties based on our initial study results. Therefore, the following Specific Aims are planned in this Project. 1. To investigate the change of blood Breg, Treg, and Toll like receptors (TLR) pathways biomarkers or the different progression among pediatric patients admitted to the PICU with the different severity of sepsis such as SIRS, sepsis, severe sepsis, and septic shock.2. To identify the roles of Breg & Treg cells, and MyD88-dependent & independent signaling pathways from mild to severe degrees in mice with sepsis induced by injection with different doses of lipopolysaccharide (LPS).3. To survey the change of these immune biomarkers in an experimental septic animal model to gain insight into serial changes of pro-inflammatory markers in innate immune response to different severity of sepsis to provide evidence for clinical application.4. To confirm the effect of the immunomodulatory properties of MSCs on regulatory B and T cells and TLR signaling pathways in mice with sepsis. Due to the important role of TLR such as TLR2 and TLR4 signaling, and regulatory cells such as Treg and Breg cells in sepsis, we investigate the effect of MSC on immunomodulation in this project by determining the difference of circulating inflammation-associated cytokine profiles and TLR activation in liver and lung tissues after different doses of MSC administration in mice with mild and severe sepsis. Importance and Novelty: This project serves as a helpful investigation to evaluate the role of TLRs signaling pathways biomarkers, and Breg and Treg in the prediction of patients with sepsis with different severity. Based on our prelimiting data, Breg, Treg, MyD88-dependent pathway, and independent pathway may show significant difference of both protein and mRNA expressions with different severity of sepsis. This project will use different doses of the different sources of MSCs via intraperitoneal injection for treating mice with mild and severe sepsis in our animal septic model by LPS ijection, and prove the immunomodulatiory effect of MSCs on sepsis. Human clinical trials thereafter can be rapidly proceeded on the basis of the results from this Project, especially when we understand that MSCs have a potential value to treat patients with sepsis.

Project IDs

Project ID:PC10708-1064
External Project ID:MOST107-2314-B182-041
Effective start/end date01/08/1831/07/19


  • sepsis
  • innate immunity
  • regulatory B cell
  • regulatory T cell
  • mesenchymal stem cells
  • immunomodulation


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