The many faces of type I interferon in systemic lupus erythematosus.

Abstract

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with a broad spectrum of clinical presentations involving multiple organ systems. An abnormal response to self-antigens is thought to drive the development of SLE; however, the factors that underlie this dysfunction are not clear. In this issue of the JCI, Li and colleagues present compelling evidence to show that type I interferons (IFNs) produced by plasmacytoid dendritic cells inhibit the clearance of apoptotic cells (ACs) by marginal zone macrophages. Specifically, type I IFNs increase the translocation of marginal zone (MZ) B cells to the follicular region of the spleen, thereby disrupting interactions between these B cells and MZ macrophages (MZMs), which in turn disrupts megakaryoblastic leukemia 1-mediated (MKL1-mediated) mechanosensing and inhibits AC phagocytosis by MZMs. The results of this study provide important insight into factors that inhibit AC clearance and promote the development of SLE.