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Tracking Regulatory T Cell Development in the Thymus Using Single-Cell RNA Sequencing/TCR Sequencing
David L Owen1,2,3, Rebecca S La Rue4, Sarah A Munro4
1Center for Immunology, University of Minnesota, Minneapolis, MN.
Journal of Immunology (Baltimore, Md. : 1950)
|August 29, 2022
Summary
Regulatory T cell progenitors (TregP) in the thymus differentiate through distinct pathways. This study reveals TregP subsets and their roles in T cell development, providing a resource for future research.
Area of Science:
- Immunology
- Developmental Biology
- T Cell Biology
Background:
- Regulatory T cells (Tregs) are crucial for immune homeostasis.
- Treg development in the thymus involves distinct progenitor subsets.
- Understanding Treg progenitor pathways is key to immune regulation.
Purpose of the Study:
- To investigate the differentiation pathways of distinct Treg progenitors (TregP) in the murine thymus.
- To characterize the transcriptomic and TCR repertoire of TregP subsets.
- To define the stages of Treg differentiation and identify key molecular drivers.
Main Methods:
- Single-cell RNA sequencing (scRNA-Seq) and TCR sequencing (TCR-Seq) were performed on sorted thymocyte populations.
- Sorted populations included double-positive (DP) thymocytes, single-positive (SP) thymocytes, and various TregP and mature Treg subsets.
- Multi-omic analysis (scRNA-Seq and bulk RNA-Seq) was used to identify distinct cellular states and gene expression patterns.
Main Results:
- Both CD25+ TregP and FOXP3lo TregP originate from an agonist-selected state, progressing through transitional stages before mature Treg differentiation.
- CD25+ TregP are a major source of Interleukin-2 (IL-2), essential for Treg maturation.
- Recirculating/resident Tregs (RT-Tregs) in the thymus are heterogeneous, exhibiting diverse TCR repertoires.
Conclusions:
- This study elucidates multiple stages of Treg differentiation within the murine thymus.
- Identifies CD25+ TregP as key IL-2 producers driving Treg development.
- Provides a comprehensive resource for understanding CD4+ thymocyte development and Treg differentiation.
