Decoding the proregenerative competence of regulatory T cells through complex tissue regeneration in zebrafish
Clin Exp Immunol, 2021 · DOI: 10.1111/cei.13661 · Published: September 7, 2021
Simple Explanation
Regulatory T cells (Tregs) are crucial for maintaining self-antigen tolerance and limiting inflammatory damage in tissues. Recent research indicates Tregs also possess direct roles in mammalian tissue repair. The regenerative capabilities of Tregs in non-mammalian vertebrates remains unexplored. Zebrafish Tregs (zTregs) rapidly migrate to injury sites, promoting the proliferation of regeneration precursor cells by producing tissue-specific regenerative factors distinct from anti-inflammatory pathways.
Key Findings
- 1Zebrafish possess two FOXP3 orthologs, foxp3a and foxp3b, potentially serving a redundant role in Treg formation and activity.
- 2Zebrafish Tregs secrete tissue-specific factors like Ntf3 for spinal cord, Nrg1 for heart, and Igf1 for retina regeneration.
- 3The proregenerative role of zebrafish Tregs is independent of their classical immunosuppressive function.
Research Summary
Practical Implications
Regenerative Therapies
Understanding the mechanisms of zTreg-mediated regeneration may lead to novel therapeutic strategies for tissue repair in humans.
Autoimmune Disease Treatment
Developing antigen-specific Treg therapy could provide a safer alternative for treating autoimmune diseases.
Inflammatory Disease Modeling
Zebrafish can be used as a model for understanding the complex mechanisms implicated in acute and chronic inflammatory diseases.
Study Limitations
- 1Zebrafish deficient in Tregs do not acquire the same fatal autoimmunity as mice lacking Treg function, potentially due to the redundancy of FoxP3b.
- 2Mouse Tregs may have lost or restricted proregenerative potential at the expense of acquiring a powerful immunosuppressive ability.
- 3The use of polyclonal Tregs can potentially suppress protective immunity against tumors and infectious diseases.