Type I interferon drives T cell cytotoxicity by upregulation of interferon regulatory factor 7 in autoimmune kidney diseases in mice

Huiying Wang, Jonas Engesser, Robin Khatri, Darius P. Schaub, Hans-Joachim Paust, Zeba Sultana, Saskia-Larissa Jauch-Speer, Anett Peters, Anna Kaffke, Stefan Bonn, Tobias B. Huber, Hans-Willi Mittrücker, Christian F. Krebs, Ulf Panzer () and Nariaki Asada ()
Additional contact information
Huiying Wang: University Medical Center Hamburg-Eppendorf
Jonas Engesser: University Medical Center Hamburg-Eppendorf
Robin Khatri: University Medical Center Hamburg-Eppendorf
Darius P. Schaub: University Medical Center Hamburg-Eppendorf
Hans-Joachim Paust: University Medical Center Hamburg-Eppendorf
Zeba Sultana: University Medical Center Hamburg-Eppendorf
Saskia-Larissa Jauch-Speer: University Medical Center Hamburg-Eppendorf
Anett Peters: University Medical Center Hamburg-Eppendorf
Anna Kaffke: University Medical Center Hamburg-Eppendorf
Stefan Bonn: University Medical Center Hamburg-Eppendorf
Tobias B. Huber: University Medical Center Hamburg-Eppendorf
Hans-Willi Mittrücker: University Medical Center Hamburg-Eppendorf
Christian F. Krebs: University Medical Center Hamburg-Eppendorf
Ulf Panzer: University Medical Center Hamburg-Eppendorf
Nariaki Asada: University Medical Center Hamburg-Eppendorf

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract In anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) and systemic lupus erythematosus (SLE), glomerulonephritis is a severe kidney complication driven by immune cells, including T cells. However, the mechanisms underlying T cell activation in these contexts remain elusive. Here we report that in patients with AAV and SLE, type I interferon (IFN-I) induces T cell differentiation into interferon-stimulated genes-expressing T (ISG-T) cells, which are characterized by an elevated IFN-I signature, an immature phenotype, and cytotoxicity in inflamed tissue. Mechanistically, IFN-I stimulates the expression of interferon regulatory factor 7 (IRF7) in T cells, which in turn induces granzyme B production. In mice, blocking IFN-I signaling reduces IRF7 and granzyme B expression in T cells, thus ameliorating glomerulonephritis. In parallel, spatial transcriptomic analyses of kidney biopsies from patients with AAV or SLE reveal an elevated ISG signature and the presence of ISG-T cells in close proximity to plasmacytoid dendritic cells, the primary producers of IFN-I. Our results from both patients and animal models thus suggest that IFN-I production in inflamed tissue may drive ISG-T cell differentiation to expand the pool of cytotoxic T cells in autoimmune diseases.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-59819-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59819-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-59819-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().