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 IFNα, but not IFNγ, 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. 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.