Obesity is known to modify the course of of autoimmune and inflammatory diseases, although the mechanisms underlying this process are not well understood.

Obesity is accompanied by a state of chronic, low-grade inflammation both systemically and within the visceral adipose tissue (VAT). Inflammatory changes in the VAT cooperate with obesity-associated dysbiosis in the gut to initiate self- or microbe-specific adaptive immune responses, generating a feed-forward inflammatory loop that dampens insulin signaling. Long-term caloric excess causes hypertrophy and ER stress in white adipocytes, leading to the release of adipokines and chemoattractants that help activate and/or recruit innate cells, such as macrophages, and adaptive immune cells, such as B and T cells, to the VAT. Obesity-associated dysbiosis contributes to increased gut permeability, facilitating leakage of microbial products and oral antigens across the gut epithelium. Together with lipid excess and dying adipocytes, these serve as potential sources of antigens and costimulatory signals for the activation of VAT B and T cells. Activated B and T cells, in turn, contribute to VAT inflammation through the secretion of inflammatory cytokines and antibodies or through cross talk with other immune cells.

Presently, how adaptive immune cells become activated during obesity, and by which antigens remain unanswered questions. This is a research area that we are super excited to pursue further. Equally interesting to us is the inflammatory circuit linking the gut to VAT and other target organs in the body during obesity and autoimmune disease. We will use combined genetic and diet approaches to tease out the important players in this circuit.