Activating autoimmunity

Why the body is sometimes attacked by its own immune system is largely a mystery. Work by Hirota et al. (page 41) suggests how an underlying genetic predisposition might combine with an environmental factor—specifically, an unrelated infection—to give rise to rheumatoid arthritis (RA) and possibly other autoimmune disorders.

A mouse model for RA, called SKG, has a single mutation in the ZAP-70 gene that causes an abundance of highly self-reactive T cells to enter the circulation. In a pathogen-free environment these mice are healthy, but when exposed to pathogens the mice develop autoimmune arthritis.

When these mice start to mount an immune response, such as that induced by a pathogen, their antigen-presenting cells (APCs) increase production of the IL-6 cytokine, the team shows. This IL-6 triggers the T cells...