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

Daniel R. Lu, Hao Wu, Ian Driver, Sarah Ingersoll, Sue Sohn, Songli Wang, Chi-Ming Li, View ORCID ProfileHyewon Phee
doi: https://doi.org/10.1101/669978
Daniel R. Lu
2Genome Analysis Unit, Amgen Research, Amgen Inc, South San Francisco, CA
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Hao Wu
1Department of Oncology and Inflammation, Amgen Research, Amgen Inc, South San Francisco, CA
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Ian Driver
2Genome Analysis Unit, Amgen Research, Amgen Inc, South San Francisco, CA
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Sarah Ingersoll
1Department of Oncology and Inflammation, Amgen Research, Amgen Inc, South San Francisco, CA
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Sue Sohn
1Department of Oncology and Inflammation, Amgen Research, Amgen Inc, South San Francisco, CA
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Songli Wang
2Genome Analysis Unit, Amgen Research, Amgen Inc, South San Francisco, CA
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Chi-Ming Li
2Genome Analysis Unit, Amgen Research, Amgen Inc, South San Francisco, CA
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  • For correspondence: hyewonp@amgen.com chimingl@amgen.com
Hyewon Phee
1Department of Oncology and Inflammation, Amgen Research, Amgen Inc, South San Francisco, CA
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  • ORCID record for Hyewon Phee
  • For correspondence: hyewonp@amgen.com chimingl@amgen.com
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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 following 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.

One Sentence Summary Single-cell analysis revealed that IL-2 mutein treatment expanded multiple sub-states of Tregs with a highly suppressive function in mice.

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Posted June 13, 2019.
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Dynamic changes in the regulatory T cell heterogeneity and function by murine IL-2 mutein
Daniel R. Lu, Hao Wu, Ian Driver, Sarah Ingersoll, Sue Sohn, Songli Wang, Chi-Ming Li, Hyewon Phee
bioRxiv 669978; doi: https://doi.org/10.1101/669978
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Dynamic changes in the regulatory T cell heterogeneity and function by murine IL-2 mutein
Daniel R. Lu, Hao Wu, Ian Driver, Sarah Ingersoll, Sue Sohn, Songli Wang, Chi-Ming Li, Hyewon Phee
bioRxiv 669978; doi: https://doi.org/10.1101/669978

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