Endosomal Toll-like receptors in clinically overt and silent autoimmunity

• Published in: Immunological reviews Vol. 269; no. 1; pp. 76 - 84
• Main Authors: Clancy, Robert M., Markham, Androo J., Buyon, Jill P.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.01.2016
• Subjects: Animals; anti-SSA/Ro60; Asymptomatic Diseases; Autoantibodies - metabolism; Autoimmunity; Endosomes - metabolism; Heart Block - immunology; Heart Block - prevention & control; Humans; Hydroxychloroquine - therapeutic use; Immunity, Maternally-Acquired; Infant, Newborn; lupus; Lupus Erythematosus, Systemic - congenital; Lupus Erythematosus, Systemic - drug therapy; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - prevention & control; neonatal lupus; Ribonucleoproteins - immunology; TLR7; Toll-Like Receptor 7 - metabolism; anti-SSA/Ro60; TLR7; autoimmunity; lupus; neonatal lupus
• ISSN: 0105-2896; 1600-065X
• DOI: 10.1111/imr.12383

Summary Toll‐like receptors (TLRs), first identified as pattern recognition receptors, are now recognized to serve as a key interface between innate and adaptive immunity. Systemic lupus erythematosus (SLE) is characterized by both continuous and cyclic stimulation of the innate and adaptive immune system by endogenous nucleic acids released from apoptotic or necrotic cells. TLR7 and TLR9 function as innate sensors of viral infection as their ligands are ssRNA and dsDNA, respectively. Recognition of self nucleic acids by endosomal TLRs in B cells and pDCs is thought to be an important step in the pathogenesis of SLE, generating anti‐nuclear antibodies and producing type I IFN. In this review, we take a specific look at how TLR7, non‐coding RNA, and SSA/Ro60 can contribute to clinical autoimmunity and organ damage in the context of neonatal lupus (NL). Although 15 times less common than SLE, NL provides a unique opportunity to study two different aspects of autoimmunity: passively acquired tissue injury in a developing fetus and clinical progression of disease in an asymptomatic mother found to have anti‐Ro60 autoantibodies only after identification of heart block/rash in a child. Finally, we discuss hydroxychloroquine (HCQ) use by asymptomatic subjects which may forestall the clinical expression of autoimmunity.