| First Author | Sun H | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 8 | Pages | 112996 |
| PubMed ID | 37598341 | Mgi Jnum | J:341186 |
| Mgi Id | MGI:7532496 | Doi | 10.1016/j.celrep.2023.112996 |
| Citation | Sun H, et al. (2023) IL-2 can signal via chemokine receptors to promote regulatory T cells' suppressive function. Cell Rep 42(8):112996 |
| abstractText | Canonical interleukin-2 (IL-2) signaling via the high-affinity CD25-containing IL-2 receptor-Janus kinase (JAK)1,3-signal transducer and activator of transcription 5 (STAT5) pathway is essential for development and maintenance of CD4(+)CD25(Hi)Foxp3(+) regulatory T cells (Tregs) that support immune homeostasis. Here, we report that IL-2 signaling via an alternative CD25-chemokine receptor pathway promotes the suppressive function of Tregs. Using an antibody against CD25 that biases IL-2 signaling toward this alternative pathway, we establish that this pathway increases the suppressive activity of Tregs and ameliorates murine experimental autoimmune encephalomyelitis (EAE). Furthermore, heparan sulfate, an IL-2-binding element of cell surfaces and extracellular matrix, or an engineered IL-2 immunocytokine can also direct IL-2 signaling toward this alternative pathway. Overall, these data reveal a non-canonical mechanism for IL-2 signaling that promotes suppressive functions of Tregs, further elucidates how IL-2 supports immune homeostasis, and suggests approaches to promote or suppress Treg functions. |
