Abstract
Tissue injury is a major cause of morbidity and mortality in SLE. Yet, there is limited knowledge of the mechanistic pathways that cause organ damage in lupus. This lack of insight hampers targeted use of current therapeutics and application of those in development. We have identified a T cell effector program associated with tissue damage in lupus nephritis, analogous to programs of effector cell development and function in states of continual antigen stimulation such as cancer and chronic infection. Our data, and by analogy, data from humans and mice with chronic infection and cancer, lead to our hypothesis, that canonical immune effector programs conserved across vertebrate evolution that are operative upon organismal insult, for example in infection or upon cellular transformation, also drive tissue injury in lupus. These programs proceed along an epigenetically regulated pathway that leads to organ injury.
