JAK-STAT signaling maintains homeostasis in T cells and macrophages

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

doi:10.1038/s41590-024-01804-1

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Title (eng)

JAK-STAT signaling maintains homeostasis in T cells and macrophages

Author

Nikolaus Fortelny

Matthias Farrik

Victoria Fife

Anna-Dorothea Gorki

Caroline Lassnig

Barbara Maurer

Katrin Meissl

Marlies Dolezal

Laura Boccuni

Aarathy Ravi Sundar Jose Geetha

Mojoyinola Joanna Akagha

Anzhelika Karjalainen

Stephen Shoebridge

Asma Farhat

Ulrike Mann

Rohit Jain

Shweta Tikoo

Nina Zila

Wolfgang Esser-Skala

Thomas Krausgruber

Katarzyna Sitnik

Thomas Penz

Anastasiya Hladik

Tobias Suske

Sophie Zahalka

Martin Senekowitsch

Daniele Barreca

Florian Halbritter

Sabine Macho-Maschler

Wolfgang Weninger

Sylvia Knapp

Thomas Decker

Mathias Müller

Christoph Bock

Abstract (eng)

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.

Keywords (eng)

Epigenetics AnalysisGene Expression AnalysisGene Regulation in Immune Cells

Type (eng)

journal article

Language

[eng]

Persistent identifier

https://phaidra.vetmeduni.ac.at/o:4300

DOI

10.1038/s41590-024-01804-1

Is in series

Title (eng)