| First Author | Fortelny N | Year | 2024 |
| Journal | Nat Immunol | Volume | 25 |
| Issue | 5 | Pages | 847-859 |
| PubMed ID | 38658806 | Mgi Jnum | J:349464 |
| Mgi Id | MGI:7645580 | Doi | 10.1038/s41590-024-01804-1 |
| Citation | Fortelny N, et al. (2024) JAK-STAT signaling maintains homeostasis in T cells and macrophages. Nat Immunol 25(5):847-859 |
| abstractText | Immune cells need to sustain a state of constant alertness over a lifetime. Yet, little is known about the regulatory processes that control the fluent and fragile balance that is called homeostasis. Here we demonstrate that JAK-STAT signaling, beyond its role in immune responses, is a major regulator of immune cell homeostasis. We investigated JAK-STAT-mediated transcription and chromatin accessibility across 12 mouse models, including knockouts of all STAT transcription factors and of the TYK2 kinase. Baseline JAK-STAT signaling was detected in CD8(+) T cells and macrophages of unperturbed mice-but abrogated in the knockouts and in unstimulated immune cells deprived of their normal tissue context. We observed diverse gene-regulatory programs, including effects of STAT2 and IRF9 that were independent of STAT1. In summary, our large-scale dataset and integrative analysis of JAK-STAT mutant and wild-type mice uncovered a crucial role of JAK-STAT signaling in unstimulated immune cells, where it contributes to a poised epigenetic and transcriptional state and helps prepare these cells for rapid response to immune stimuli. |
