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Dynamic changes in the regulatory T-cell heterogeneity and function by murine IL-2 mutein.

ABSTRACT: The therapeutic expansion of Foxp3+ regulatory T cells (Tregs) shows promise for treating autoimmune and inflammatory disorders. Yet, how this treatment affects the heterogeneity and function of Tregs is not clear. Using single-cell RNA-seq analysis, we characterized 31,908 Tregs from the mice treated with a half-life extended mutant form of murine IL-2 (IL-2 mutein, IL-2M) that preferentially expanded Tregs, or mouse IgG Fc as a control. Cell clustering analysis revealed that IL-2M specifically expands multiple sub-states of Tregs with distinct expression profiles. TCR profiling with single-cell analysis uncovered Treg migration across tissues and transcriptional changes between clonally related Tregs after IL-2M treatment. Finally, we identified IL-2M-expanded Tnfrsf9+Il1rl1+ Tregs with superior suppressive function, highlighting the potential of IL-2M to expand highly suppressive Foxp3+ Tregs.

SUBMITTER: Lu DR

PROVIDER: S-EPMC7156283 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Dynamic changes in the regulatory T-cell heterogeneity and function by murine IL-2 mutein.

Lu Daniel R DR Wu Hao H Driver Ian I Ingersoll Sarah S Sohn Sue S Wang Songli S Li Chi-Ming CM Phee Hyewon H

Life science alliance 20200408 5

The therapeutic expansion of Foxp3<sup>+</sup> regulatory T cells (Tregs) shows promise for treating autoimmune and inflammatory disorders. Yet, how this treatment affects the heterogeneity and function of Tregs is not clear. Using single-cell RNA-seq analysis, we characterized 31,908 Tregs from the mice treated with a half-life extended mutant form of murine IL-2 (IL-2 mutein, IL-2M) that preferentially expanded Tregs, or mouse IgG Fc as a control. Cell clustering analysis revealed that IL-2M s ...[more]

PMID: 32269069

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Dynamic changes in the regulatory T cell heterogeneity and function by murine IL-2 mutein

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