Adipose tissue harbors pathogenic T cells in obesity that exacerbate inflammatory arthritis.

Summary

In an antigen-induced arthritis model, obesity drives visceral adipose tissue (VAT) as a niche where CD8+ T cells expand under IFNα signaling and aggravate arthritis. VAT transplantation exacerbated disease, IFNα (but not IFNγ) expanded VAT CD8+ T cells, and T cell–specific Ifnar1 deletion attenuated arthritis in obese mice, establishing an adipose–immune axis linking obesity to autoimmunity.

Key Findings

• Obesity (HFD) promotes homing and expansion of arthritis-inducing CD8+ OT-I T cells within visceral adipose tissue (VAT).
• VAT transplantation from arthritic mice worsened arthritis in recipients; disease was ameliorated by CD8+ T cell depletion.
• IFNα (but not IFNγ) expanded VAT CD8+ T cells; global and T cell–specific Ifnar1 deletion reduced VAT CD8+ expansion and arthritis severity.

Clinical Implications

Targeting IFNα/IFNAR signaling or adipose-resident CD8+ T cells may mitigate arthritis severity in obese patients; prioritizing weight reduction could reduce autoimmune disease burden via immunologic mechanisms.

Limitations

• Findings are preclinical and based on mouse antigen-induced arthritis models.
• Human VAT T cell phenotypes and translatability to diverse autoimmune diseases remain untested.

Future Directions

Profile adipose-resident T cells in obese patients with arthritis; test IFNAR pathway inhibitors or anti-IFNα strategies in obesity-associated autoimmunity; examine whether weight loss modulates VAT T cell programs and disease activity.