Adipose tissue harbors pathogenic T cells in obesity that exacerbate inflammatory arthritis
Abstrak
Obesity worsens inflammatory arthritis severity, even in non-load–bearing joints, but the mechanism is unknown. Here, we show that there is an immunological mechanism mediated by T cells in adipose tissue. Using an antigen-induced arthritis model with trackable, arthritis-inducing CD8+ OT-I T cells, we found that OT-I T cells home to visceral adipose tissue (VAT) and expand there in the obese high-fat diet (HFD) context. Transplant of VAT from arthritic mice increased arthritis severity in naïve recipient mice and was ameliorated by CD8 T cell depletion. Bulk RNA sequencing identified pro-inflammatory changes to OT-I T cells in VAT characterized by increased IFN α and γ signaling after HFD. Intraperitoneal injection of IFNα, but not IFNγ, expanded CD8 T cell numbers in VAT. HFD-induced expansion of VAT CD8 T cells was ameliorated with global Ifnar1 deletion, and importantly, genetic deletion of Ifnar1 in T cells decreased arthritis severity in obese mice. These results provide a mechanistic explanation of how obesity worsens autoimmunity.
Penulis (9)
Heather J. Faust
Margaret H. Chang
A. Helena Jonsson
Erin Theisen
Nelson M. LaMarche
William V. Trim
Lydia Lynch
Peter A. Nigrovic
Michael B. Brenner
Akses Cepat
- Tahun Terbit
- 2025
- Bahasa
- en
- Total Sitasi
- 3×
- Sumber Database
- CrossRef
- DOI
- 10.1084/jem.20240677
- Akses
- Open Access ✓