Toll-Like Receptor Pathways in Autoimmune Diseases

• Published in: Clinical Reviews in Allergy & Immunology Vol. 50; no. 1; pp. 1 - 17
• Main Authors: Chen, Ji-Qing, Szodoray, Peter, Zeher, Margit
• Format: Journal Article Book Review
• Language: English
• Published: New York Springer US 01.02.2016; Springer; Springer Nature B.V
• Subjects: Allergology; Animals; Autoimmune Diseases - diagnosis; Autoimmune Diseases - etiology; Autoimmune Diseases - metabolism; B cells; Carrier Proteins - genetics; Carrier Proteins - metabolism; Gene expression; Genetic Predisposition to Disease; Genetic research; Humans; Immunology; Internal Medicine; Lupus; Medicine; Medicine & Public Health; Membrane proteins; Multigene Family; Polymorphism, Single Nucleotide; Protein Binding; Scleroderma (Disease); Signal Transduction; Single nucleotide polymorphisms; Systemic lupus erythematosus; Toll-Like Receptors - chemistry; Toll-Like Receptors - genetics; Toll-Like Receptors - metabolism; Suppressor of cytokine signaling (SOCS); Autoimmune disease; Toll-like receptors (TLRs); IL-1-receptor-associated kinase (IRAK); TNF-receptor-associated factor (TRAF)
• ISSN: 1080-0549; 1559-0267
• DOI: 10.1007/s12016-015-8473-z

Autoimmune diseases are a family of chronic systemic inflammatory disorders, characterized by the dysregulation of the immune system which finally results in the break of tolerance to self-antigen. Several studies suggest that Toll-like receptors (TLRs) play an essential role in the pathogenesis of autoimmune diseases. TLRs belong to the family of pattern recognition receptors (PRRs) that recognize a wide range of pathogen-associated molecular patterns (PAMPs). TLRs are type I transmembrane proteins and located on various cellular membranes. Two main groups have been classified based on their location; the extracelluar group referred to the ones located on the plasma membrane while the intracellular group all located in endosomal compartments responsible for the recognition of nucleic acids. They are released by the host cells and trigger various intracellular pathways which results in the production of proinflammatory cytokines, chemokines, as well as the expression of co-stimulatory molecules to protect against invading microorganisms. In particular, TLR pathway-associated proteins, such as IRAK, TRAF, and SOCS, are often dysregulated in this group of diseases. TLR-associated gene expression profile analysis together with single nucleotide polymorphism (SNP) assessment could be important to explain the pathomechanism driving autoimmune diseases. In this review, we summarize recent findings on TLR pathway regulation in various autoimmune diseases, including Sjögren’s syndrome (SS), systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), systemic sclerosis (SSc), and psoriasis.