Systemic autoimmunity caused by fas deficiency in macrophages: A new perspective on the first identified autoimmunity gene

摘要

Fas was identified as the first "autoimmunity gene" 2 decades ago (1). Although Fas was shown to mediate apoptosis, the detailed mechanism as to how its deficiency drives the development of autoimmunity has remained a fascinating but unresolved issue. On the one hand, the involvement of Fas-mediated apoptosis in the regulation of a multitude of immune responses suggested the possibility that the autoimmunity reflected a collection of defective responses, but on the other hand, the clustering of phenotypes suggested the possibility that the defect acted primarily through a single, crucial event that had repercussions on a multitude of responses. In a study reported in this issue of Arthritis & Rheumatism, Cuda and colleagues (2) identified such an event. However, contemporary understanding of the modulatory effects of immune cells suggests that specific targeting of immune cell subpopulations will be necessary for the application of Fas as safe and effective apoptosis therapy.