Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by abnormal function of both the innate and the adaptive immune system, leading to a loss of tolerance to self-antigens. Monocytes are a key component of the innate immune system and are efficient producers of multiple cytokines. In SLE, inappropriate activation of monocytes is thought to contribute to the loss of self-tolerance. In this study, we demonstrate that type 1 interferon (IFN) production by CpG-challenged monocytes can be suppressed by C1q through activate leukocyte-associated Ig-like receptor-1 (LAIR-1), which contains ITIM motifs. The phosphorylation of LAIR-1 and the interaction of LAIR-1 with SHP-1 were enhanced following LAIR-1 engagement by C1q. Moreover, engagement of LAIR-1 by C1q inhibited nuclear translocation of interferon regulatory factors IRF-3 and IRF-5 in CpG-stimulated monocytes. These data suggest a model in which LAIR-1 engagement by C1q helps maintain monocyte tolerance, specifically with respect to toll-like receptor-9 (TLR9)-mediated monocyte activation.
Faculty; Northwell Researcher
School of Medicine; Northwell Health
General Internal Medicine