Regulatory T cell heterogeneity: who they are, where they come from, and where they go
- 1Cell Therapy Advanced Technologies, Oncology R&D, AstraZeneca
- 2Bioscience Immunology, Research and Early Development, Respiratory and Immunology, Biopharmaceuticals R&D, AstraZeneca
Abstract
Regulatory T cells (Tregs) are essential for enforcing immune tolerance and homeostasis, but they comprise several distinct populations that differ in developmental origin, activation state, tissue adaptation, and functional specialization. These differences shape where Tregs reside, which immune responses they suppress, and how stable their lineage remains over time. This heterogeneity matters increasingly as immunology and therapeutics move from bulk Treg measurements toward subset- and context-specific interpretations. Treg-directed strategies now range from expanding Tregs to treat autoimmune disease to inhibiting tumor Tregs to enhance tumor immunity. In this review, we use three questions (who heterogeneous Tregs are, where they come from, and where they go) to organize recent advances that explain how Tregs are generated and maintained, how they traffic and adapt across tissues, and how their states shift across physiology and diseases. We also delineate Treg heterogeneity with a particular focus on contrasts between naïve Tregs (nTregs) and effector Tregs (eTregs), including defining markers and key biological features. We aim to provide a practical framework for interpreting human Treg datasets and for selectively using distinct Treg subsets in experimental design and therapeutic development.
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BibTeX
@article{yang2026regulatory,
title = {{Regulatory T cell heterogeneity: who they are, where they come from, and where they go}},
author = {Fan Yang and Yasuhiro Ikeda and Zengli Guo and Kyle J. Bednar},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1929923},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1929923/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Regulatory T cell heterogeneity: who they are, where they come from, and where they go
AU - Fan Yang
AU - Yasuhiro Ikeda
AU - Zengli Guo
AU - Kyle J. Bednar
PY - 2026
DA - 2026/10/09
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1929923
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1929923/full
AB - Regulatory T cells (Tregs) are essential for enforcing immune tolerance and homeostasis, but they comprise several distinct populations that differ in developmental origin, activation state, tissue adaptation, and functional specialization. These differences shape where Tregs reside, which immune responses they suppress, and how stable their lineage remains over time. This heterogeneity matters increasingly as immunology and therapeutics move from bulk Treg measurements toward subset- and context-specific interpretations. Treg-directed strategies now range from expanding Tregs to treat autoimmune disease to inhibiting tumor Tregs to enhance tumor immunity. In this review, we use three questions (who heterogeneous Tregs are, where they come from, and where they go) to organize recent advances that explain how Tregs are generated and maintained, how they traffic and adapt across tissues, and how their states shift across physiology and diseases. We also delineate Treg heterogeneity with a particular focus on contrasts between naïve Tregs (nTregs) and effector Tregs (eTregs), including defining markers and key biological features. We aim to provide a practical framework for interpreting human Treg datasets and for selectively using distinct Treg subsets in experimental design and therapeutic development.
SN - 1664-3224
ER -