TY - JOUR T1 - Dynamic changes in the regulatory T-cell heterogeneity and function by murine IL-2 mutein JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.201900520 VL - 3 IS - 5 SP - e201900520 AU - Daniel R Lu AU - Hao Wu AU - Ian Driver AU - Sarah Ingersoll AU - Sue Sohn AU - Songli Wang AU - Chi-Ming Li AU - Hyewon Phee Y1 - 2020/05/01 UR - https://www.life-science-alliance.org/content/3/5/e201900520.abstract N2 - 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. ER -