Elsevier

Science Bulletin

Volume 65, Issue 13, 15 July 2020, Pages 1114-1124
Science Bulletin

Article
Single-cell RNA-seq unveils critical regulators of human FOXP3+ regulatory T cell stability

https://doi.org/10.1016/j.scib.2020.01.002Get rights and content
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open access

Abstract

The heterogeneity and plasticity of T lymphocytes is critical for determining immune response outcomes. Functional regulatory T (Treg) cells are commonly characterized by stable FOXP3 expression and have reported to exhibit heterogeneous phenotypes under inflammatory conditions. However, the interplay between inflammation and Treg cell suppressive activity still remains elusive. Here, we utilized single-cell RNA sequencing to investigate how human Treg cells respond to the pro-inflammatory cytokine interleukin-6 (IL-6). We observed that Treg cells divided into two subpopulations after IL-6 stimulation. TIGIT unstable Treg cells lost FOXP3 expression and gained an effector-like T cell phenotype, whereas TIGIT+ Treg cells retained robust suppressive function. Single cell transcriptome analysis revealed a spectrum of cellular states of IL-6-stimulated Treg cells and how cytochrome P450 family 1 subfamily A member 1 (CYP1A1) is a crucial regulator of Treg cell suppressive capability and stability. CYP1A1-deficient human Treg cells developed a Th17-like phenotype after IL-6 stimulation. Our findings implicate CYP1A1 as a previously unidentified regulator of Treg cells that may have target potential for clinical application for biotherapies.

Keywords

Treg cell
scRNA-seq
Inflammation
Interleukin-6
Heterogeneity
Cytochrome P450 1A1

Cited by (0)

Gang Yi, graduate student at Shanghai University and Institut Pasteur of Shanghai, Chinese Academy of Sciences. His research interest focuses on the single-cell sequencing and functional analysis of regulatory T cells in inflammation and tumor environment.

Yi Zhao, graduated from South China University of Technology. Dr. Zhao is engaged in basic research on immune microenvironment and regulatory T cells. In recent years, he has conducted in-depth research on the stability of regulatory T cells under inflammatory conditions, single cell analysis and regulation of immune microenvironment.

Feng Xie, Ph.D. student from Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine. She focuses on the study of immune cell heterogeneity in tumor microenvironment using single-cell sequencing.

Xiao Liu is currently an adjunct professor of Northwest University and a Ph.D. supervisor in University of Chinese Academy of Sciences. His research interests are translational researches in Cancer and immunological diseases, and T/B cell biomarker discovery in disease diagnosis and progression.

Bin Li, professor at Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine. Research in Dr. Li’s laboratory mainly focuses on understanding molecular mechanism underlying the functional stability, plasticity and balance of FOXP3+ Regulatory T cells (Treg).

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These authors contributed equally to this work.