Visceral adipose tissue harbors pathogenic T cells in obesity that exacerbate inflammatory arthritis

Obesity worsens inflammatory arthritis severity, even in non-load bearing joints, but the mechanism is unknown. Here, we show that there is an immunological link mediated by T cells in adipose tissue and arthritis pathogenesis. Using an antigen-induced arthritis model with trackable, arthritis-inducing OT-I T cells, we found that OT-I T cells home to visceral adipose tissue (VAT) after arthritis induction and expand in the obese high-fat diet (HFD) context. Transplant of visceral adipose tissue from arthritic mice increased arthritis severity in naïve mice and was ameliorated by CD8 depletion. Bulk RNA-sequencing identified pro-inflammatory changes to OT-I T cells residing in peripheral lymph nodes and VAT characterized by increased interferon signaling after HFD. Intra-peritoneal injection of IFNa, but not IFN?, expanded CD8 VAT T cell numbers. Using IFNAR1 blocking antibodies or IFNAR1-deficient mice confirmed that the increased number of CD8 T cells in VAT following HFD was IFNAR1 dependent. Our results show that VAT is a depot which can support a Type-1 interferon-driven expansion of a pool of CD8 T cells during obesity that are readily available to increase arthritic inflammation. These mechanisms may contribute to the increased frequency and severity of autoimmune diseases in obese patients. Overall design: Comparative gene expression profiling analysis of bulk RNA-seq data for mouse lymph node or visceral adipose derived T cells from OT-I mice on lean or high fat diet for 8 weeks. Cells were cultured overnight before sorting a pure T cell population.