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bioRxiv · 10.1101/669978

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

Lu, D. R.·Wu, H.·Driver, I.·Ingersoll, S.·Sohn, S.·Wang, S.·Li, C.-M.·Phee, H.
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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.\n\nOne Sentence SummarySingle-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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Lu, D. R., Wu, H., Driver, I., Ingersoll, S., Sohn, S., Wang, S., Li, C.-M., Phee, H.. 2019-06-13. Dynamic changes in the regulatory T cell heterogeneity and function by murine IL-2 mutein. https://doi.org/10.1101/669978

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