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Updated: Aug 20, 2025
Accelerated Type 1 Diabetes Induction in Mice by Adoptive Transfer of Diabetogenic CD4+ T Cells
Published on: May 6, 2013
Paeoniflorin protects NOD mice from T1D through regulating gut microbiota and TLR4 mediated myD88/TRIF pathway
Cheng Luo1, Danyi Yang2, Can Hou3
1Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, PR China.
Abstract:
This study aimed to explore the effect of PF in regulating the progression of T1D through regulating gut microbiota and inhibiting TLR4-myD88/TRIF pathway. T1D mouse models were established and received PF treatment through intraperitoneal injection. The glucose, sugar tolerance, the incidence of T1D and H&E staining were detected to verify the effect of PF on T1D. Meanwhile, the changes of gut microbiota and the permeability of intestines in mice were also measured. On parallel, the number and function of immune cells were detected by Flow Cytometry. The expressions of ZO-1, ZO-2 and TLR4-myD88/TRIF pathway related proteins were detected by western blotting. Mice received PF treatment had decreased incidence of T1D and inflammatory infiltration in islet tissues compared with those received PBS treatment. In addition to that, PF treated mice had increased Sutterella species and decreased intestinal permeability, in which the decreased ratio of Th1/Th17 and increased Treg cells were also identified. The expression of TLR4-myD88/TRIF pathway was also suppressed in response to PF treatment. Moreover, further treatment with TLR4 agonist, LPS, could reverse the effect of PF on T1D mice. PF can suppress the TLR4 mediated myD88/TRIF pathway to change the distribution of gut microbiota, so as to protect NOD mice from T1D.
Insights
PF treatment reduced Type 1 Diabetes (T1D) incidence in mice by modulating gut bacteria and inhibiting the TLR4-myD88/TRIF pathway. This approach also decreased intestinal permeability and inflammation.
Area of Science:
- Immunology
- Microbiology
- Endocrinology
Background:
- Type 1 Diabetes (T1D) is an autoimmune disease characterized by pancreatic beta-cell destruction.
- The gut microbiota and the Toll-like receptor 4 (TLR4) pathway are implicated in T1D pathogenesis.
- Identifying therapeutic strategies targeting these pathways is crucial for T1D management.
Purpose of the Study:
- To investigate the therapeutic potential of PF in a mouse model of T1D.
- To elucidate the mechanisms by which PF influences T1D progression, focusing on gut microbiota and the TLR4-myD88/TRIF pathway.
Main Methods:
- T1D mouse models were established and treated with PF via intraperitoneal injection.
- Evaluated T1D incidence, glucose metabolism, gut microbiota composition, intestinal permeability, immune cell profiles, and protein expression related to the TLR4 pathway.
- Western blotting and Flow Cytometry were employed for molecular and cellular analyses.
Main Results:
- PF treatment significantly reduced T1D incidence and insulitis compared to controls.
- PF administration altered gut microbiota, increasing Sutterella species and decreasing intestinal permeability.
- PF suppressed the TLR4-myD88/TRIF pathway, reduced Th1/Th17 cells, and increased regulatory T cells (Treg).
- TLR4 agonist (LPS) treatment reversed the protective effects of PF.
Conclusions:
- PF demonstrates a protective effect against T1D in mice.
- PF acts by suppressing the TLR4-mediated myD88/TRIF pathway, altering gut microbiota composition, and restoring immune balance.
- PF represents a potential therapeutic agent for T1D by targeting gut dysbiosis and immune dysregulation.
