Insulin-like Growth Factor-1 Synergizes with IL-2 to Induce Homeostatic Proliferation of Regulatory T cells

Journal article

Melanie R. Shapiro, Leeana D. Peters, Matthew E Brown, C. Cabello-Kindelan, A. Posgai, A. Bayer, T. Brusko
bioRxiv, 2022

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APA Click to copy
Shapiro, M. R., Peters, L. D., Brown, M. E., Cabello-Kindelan, C., Posgai, A., Bayer, A., & Brusko, T. (2022). Insulin-like Growth Factor-1 Synergizes with IL-2 to Induce Homeostatic Proliferation of Regulatory T cells. BioRxiv.

Chicago/Turabian Click to copy
Shapiro, Melanie R., Leeana D. Peters, Matthew E Brown, C. Cabello-Kindelan, A. Posgai, A. Bayer, and T. Brusko. “Insulin-like Growth Factor-1 Synergizes with IL-2 to Induce Homeostatic Proliferation of Regulatory T Cells.” bioRxiv (2022).

MLA Click to copy
Shapiro, Melanie R., et al. “Insulin-like Growth Factor-1 Synergizes with IL-2 to Induce Homeostatic Proliferation of Regulatory T Cells.” BioRxiv, 2022.

BibTeX Click to copy

@article{melanie2022a,
  title = {Insulin-like Growth Factor-1 Synergizes with IL-2 to Induce Homeostatic Proliferation of Regulatory T cells},
  year = {2022},
  journal = {bioRxiv},
  author = {Shapiro, Melanie R. and Peters, Leeana D. and Brown, Matthew E and Cabello-Kindelan, C. and Posgai, A. and Bayer, A. and Brusko, T.}
}

Abstract

IL-2 has been proposed to restore tolerance via regulatory T cell (Treg) expansion in autoimmunity, yet off-target effects necessitate identification of a combinatorial approach. We recently reported reduced levels of immunoregulatory insulin-like growth factor-1 (IGF1) during type 1 diabetes (T1D) progression. Thus, we hypothesized that IGF1 would synergize with IL-2 to expand Tregs. We observed IGF1R was elevated on murine memory and human naïve Treg subsets. IL-2 and IGF1 promoted murine PI3K/Akt and human STAT5 signaling in Tregs. IL-2 and IGF1 treatment expanded Tregs beyond either agent alone in NOD mice. Incubation of naïve human CD4+ T cells with IL-2 and IGF1 enhanced Treg proliferation in vitro, without the need for T cell receptor ligation. This synergism was attributed to increased high-affinity IL-2Rα expression on naïve Tregs, in contrast to intermediate-affinity IL-2Rβ and IL-2Rγ subunit enhancement on naïve conventional T cells (Tconv). We then demonstrated that IGF1 and IL-2 or the IL2Rγ-chain-dependent cytokine, IL-7, can be used to induce proliferation of genetically-engineered naïve Treg or Tconv cells, respectively. These data support the potential use of IGF1 in combination with common γ-chain cytokines to drive T cell expansions both in vitro and in vivo for cellular therapeutics and genetic modifications.