A Murine Autoimmune Model of Rheumatoid Arthritis and Systemic Lupus Erythematosus Associated with Deregulated Production of IL-17 and IL-21

Abstract

T-helper cell 17 (Th17) cells play an important role in the pathogenesis of many autoimmune disorders including Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE). In this chapter we describe a murine model where deregulated production of IL-17 and IL-21 can lead to either lupus-like disease or RA-like symptoms depending on the genetic background. We delineate the key techniques that can be used to dissect the mechanisms responsible for the pathogenesis of these diseases at both a cellular and molecular level including in vitro Th17 cell differentiation, chromatin immunoprecipitation assays, and retroviral transduction experiments. We also describe the methodologies that can be utilized to monitor the classic clinical findings of RA and SLE in murine models. Given the broad involvement of deregulated production of IL-17 and IL-21 in autoimmunity, many of these techniques could also be valuable for the investigation of these pathways in murine models of other autoimmune diseases.