| First Author | Hatzioannou A | Year | 2020 |
| Journal | Nat Immunol | Volume | 21 |
| Issue | 1 | Pages | 75-85 |
| PubMed ID | 31844326 | Mgi Jnum | J:290128 |
| Mgi Id | MGI:6435313 | Doi | 10.1038/s41590-019-0555-2 |
| Citation | Hatzioannou A, et al. (2020) An intrinsic role of IL-33 in Treg cell-mediated tumor immunoevasion. Nat Immunol 21(1):75-85 |
| abstractText | Regulatory T (Treg) cells accumulate into tumors, hindering the success of cancer immunotherapy. Yet, therapeutic targeting of Treg cells shows limited efficacy or leads to autoimmunity. The molecular mechanisms that guide Treg cell stability in tumors remain elusive. In the present study, we identify a cell-intrinsic role of the alarmin interleukin (IL)-33 in the functional stability of Treg cells. Specifically, IL-33-deficient Treg cells demonstrated attenuated suppressive properties in vivo and facilitated tumor regression in a suppression of tumorigenicity 2 receptor (ST2) (IL-33 receptor)-independent fashion. On activation, Il33(-/-) Treg cells exhibited epigenetic re-programming with increased chromatin accessibility of the Ifng locus, leading to elevated interferon (IFN)-gamma production in a nuclear factor (NF)-kappaB-T-bet-dependent manner. IFN-gamma was essential for Treg cell defective function because its ablation restored Il33(-/-) Treg cell-suppressive properties. Importantly, genetic ablation of Il33 potentiated the therapeutic effect of immunotherapy. Our findings reveal a new and therapeutically important intrinsic role of IL-33 in Treg cell stability in cancer. |
