Zeitschriftenaufsatz | 2024 Open Access

JAK-STAT signaling maintains homeostasis in T cells and macrophages

Autor:in

Fortelny, Nikolaus; Farlik, Matthias; Fife, Victoria; Gorki, Anna-Dorothea; Lassnig, Caroline; Maurer, Barbara; Meissl, Katrin; Dolezal, Marlies; Boccuni, Laura; Geetha, Aarathy Ravi Sundar Jose; Akagha, Mojoyinola Joanna; Karjalainen, Anzhelika; Shoebridge, Stephen; Farhat, Asma; Mann, Ulrike; Jain, Rohit; Tikoo, Shweta; Zila, Nina; Esser-Skala, Wolfgang; Krausgruber, Thomas; Sitnik, Katarzyna M.; Penz, Thomas; Hladik, Anastasiya; Suske, Tobias; Zahalka, Sophie; Senekowitsch, M.; Barreca, Daniele; Halbritter, Florian; Macho-Maschler, Sabine; Weninger, Wolfgang; Neubauer, Heidi; Moriggl, Richard; Knapp, Sylvia; Sexl, Veronika; Strobl, Birgit; Decker, T.; Mueller, Mathias; Bock, Christoph

Publikationen als Autor:in / Herausgeber:in der Vetmeduni

Neubauer-Sedy, Heidi; Müller, Mathias; Dolezal, Marlies; Lassnig, Caroline; Strobl, Birgit; Sitnik, Katarzyna Maria; Sexl, Veronika; Suske, Tobias; Macho-Maschler, Sabine

Journal

Nature Immunology

Abstrakt

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. Bock and colleagues perform integrative analysis of JAK-STAT mutant mice and find JAK-STAT signaling regulates CD8+ T cell and macrophage homeostasis by contributing to a poised epigenetic and transcription-regulatory state, preparing cells to rapidly respond to stimuli.

Schlagwörter

Animals; Homeostasis; Signal Transduction; Mice; Macrophagesimmunologymetabolism; Janus Kinasesmetabolism; Mice, Knockout; STAT Transcription Factorsmetabolism; CD8-Positive T-Lymphocytesimmunologymetabolism; STAT1 Transcription Factormetabolismgenetics; Mice, Inbred C57BL; Interferon-Stimulated Gene Factor 3, gamma Subunitmetabolismgenetics; TYK2 Kinasemetabolismgenetics; Gene Expression Regulation

Dokumententyp

Originalarbeit

CC Lizenz

CCBY

Open Access Type

Hybrid

ISSN/eISSN

1529-2908 - 1529-2916

DOI

10.1038/s41590-024-01804-1