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

Regenerative Medicine Immunology Research Methodology & Design

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.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Zebrafish possess two FOXP3 orthologs, foxp3a and foxp3b, potentially serving a redundant role in Treg formation and activity.
2
Zebrafish Tregs secrete tissue-specific factors like Ntf3 for spinal cord, Nrg1 for heart, and Igf1 for retina regeneration.
3
The proregenerative role of zebrafish Tregs is independent of their classical immunosuppressive function.

Research Summary

This review explores the proregenerative roles of Tregs in zebrafish and mammals, highlighting the FoxP3-dependent immunosuppressive function of Tregs in zebrafish as a useful model for future research. Tregs regulate both innate and adaptive immune systems to facilitate tissue repair by inflammatory modulation, influencing neutrophil activity, macrophage polarization, and T cell-mediated inflammation. Zebrafish Tregs play a pivotal role in the proliferation of neural progenitor cells by secreting neurogenic factors in the injury-induced spinal cord, facilitating spinal cord regeneration.

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

1
Zebrafish deficient in Tregs do not acquire the same fatal autoimmunity as mice lacking Treg function, potentially due to the redundancy of FoxP3b.
2
Mouse Tregs may have lost or restricted proregenerative potential at the expense of acquiring a powerful immunosuppressive ability.
3
The use of polyclonal Tregs can potentially suppress protective immunity against tumors and infectious diseases.

Your Feedback

Was this summary helpful?

Back to Regenerative Medicine