Cornelia M. Weyand, MD, PhD
Mayo Clinic School of Medicine and Stanford University
Rochester, MN, United States
Disclosure(s): AbbVie/Abbott: Advisor or Review Panel Member (Ongoing); Bristol-Myers Squibb(BMS): Advisor or Review Panel Member (Ongoing); Gilead: Advisor or Review Panel Member (Ongoing); Novartis: Advisor or Review Panel Member (Ongoing)
Why the immune system of patients with rheumatoid arthritis loses self-tolerance and induces chronic destructive inflammation remains undefined. A hallmark of the immune system in patients with rheumatoid arthritis is the accumulation of aged T cells, which give rise to inflammatory immune effector cells that have high tissue invasiveness, produce copious amounts of inflammatory cytokines and trigger tissue inflammation through pyroptotic cell death. Cellular and molecular studies conducted over the last decade have defined the underling mechanisms, revealing a critical position for mitochondria and cellular metabolism in abnormal immune effector cells. Specifically, T cells in rheumatoid arthritis have defects in the electron transport chain and the Krebs cycle, leading to energy depletion and miscommunication with other organelles. Deficiency of mitochondrial aspartate triggers expansion of endoplasmic reticulum membranes, fueling hyperproduction of TNF, a crucial cytokine in rheumatoid arthritis. Mitochondrial failure is a key feature of cellular aging, closing the loop of premature immune aging and loss of self-tolerance in rheumatoid arthritis.
Speaker: Cornelia M. Weyand, MD, PhD – Mayo Clinic School of Medicine and Stanford University
