Although in vitro observations indicate that long noncoding RNAs (lncRNAs) regulate innate immune responses, their effect upon immune tolerance in vivo has not been defined.  We have identified a novel gene of unknown function for which sequence variation is associated with autoimmune diabetes in the nonobese diabetic (NOD) mouse strain.  Bioinformatics and expression analyses indicate this gene encodes a lncRNA that is induced by Toll-like receptor (TLR) activation, localises to the nucleus and cytoplasm of dendritic cells, and binds to proteins within these cellular compartments.  Moreover, sequence variation for this gene is associated with altered TLR-mediated cytokine production.  Hence this gene was named Apics for Attenuator of Pattern recognition receptor-Induced Cytokine Secretion.  To further investigate the function of this lncRNA, we established a C57BL/6 (B6) knockout mouse strain for Apics and discovered that Apics-deficient dendritic cells exhibit enhanced TLR-mediated cytokine production.  Apics-deficient B6 mice also exhibit increased susceptibility to autoimmunity in two disease models:  experimental autoimmune encephalomyelitis and experimental anti-neutrophil cytoplasmic antibody-associated vasculitis.  Our study suggests that lncRNAs, such as Apics, can serve as TLR-inducible repressors that regulate the magnitude of innate immune responses to reduce the risk for developing autoimmune disease.