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Analysis of therapeutic potential of preclinical models based on DR3/TL1A pathway modulation (Review)
Yunhong Yu1, Peng Jiang1, Pan Sun1
1Institute of Blood Transfusion, Chinese Academy of Medical Science and Peking Union Medical College, Chengdu, Sichuan 610052, P.R. China.
Abstract:
Death receptor 3 (DR3) and its corresponding ligand, tumor necrosis factor-like ligand 1A (TL1A), belong to the tumor necrosis factor superfamily. Signaling via this receptor-ligand pair results in pro-inflammatory and anti-inflammatory effects. Effector lymphocytes can be activated to exert pro-inflammatory activity by triggering the DR3/TL1A pathway. By contrast, DR3/TL1A signaling also induces expansion of the suppressive function of regulatory T cells, which serve an important role in exerting anti-inflammatory functions and maintaining immune homeostasis. Preclinical evidence indicates that neutralizing and agonistic antibodies, as well as ligand-based approaches targeting the DR3/TL1A pathway, may be used to treat diseases, including inflammatory and immune-mediated diseases. Accumulating evidence has suggested that modulating the DR3/TL1A pathway is a promising therapeutic approach for patients with these diseases. This review discusses preclinical models to gauge the progress of therapeutic strategies for diseases involving the DR3/TL1A pathway to aid in drug development.
Insights
The Death Receptor 3 (DR3) and TL1A pathway has dual roles in inflammation and immune regulation. Modulating this pathway shows promise for treating inflammatory and immune-mediated diseases.
Area of Science:
- Immunology
- Molecular Biology
- Pharmacology
Background:
- Death Receptor 3 (DR3) and its ligand, Tumor Necrosis Factor-like Ligand 1A (TL1A), are key members of the TNF superfamily.
- DR3/TL1A signaling elicits both pro-inflammatory and anti-inflammatory responses.
- This pathway influences effector lymphocyte activation and regulatory T cell function, impacting immune homeostasis.
Purpose of the Study:
- To review preclinical models evaluating therapeutic strategies targeting the DR3/TL1A pathway.
- To assess the progress of drug development for diseases involving DR3/TL1A signaling.
Main Methods:
- Review of preclinical evidence and therapeutic approaches.
- Analysis of ligand-based strategies and antibody therapies (neutralizing and agonistic).
Main Results:
- DR3/TL1A pathway modulation is a promising therapeutic strategy.
- Preclinical data supports the use of DR3/TL1A targeting for inflammatory and immune-mediated diseases.
Conclusions:
- Targeting the DR3/TL1A pathway offers potential for treating various diseases.
- Further development of therapeutic strategies is warranted based on preclinical models.
