Toll-Like Receptors Gene Polymorphisms in Autoimmune Disease

Abstract

Toll-like receptors (TLRs) are important initiators of the immune response, both innate and acquired. Evidence suggests that gene polymorphisms within TLRs cause malfunctions of certain key TLR-related signaling pathways, which subsequently increases the risk of autoimmune diseases. We illustrate and discuss the current findings on the role of Toll-like receptor gene polymorphisms in numerous autoimmune diseases in this review, such as type 1 diabetes mellitus, Graves' disease, rheumatoid arthritis, systemic lupus erythematosus and multiple sclerosis. The study of genetic variation in TLRs in different populations has shown a complex interaction between immunity and environmental factors. This interaction suggests that TLR polymorphisms affect the susceptibility to autoimmune diseases differently in various populations. The identification of Toll-like receptor gene polymorphisms can expand our understanding of the pathogenesis of autoimmune diseases, which will subsequently guide effective medical management and provide insight into prognosis and advanced treatments.

Keywords: autoimmune disease; gene polymorphisms; pathogenesis; toll-like receptors; treatment.

Figure 1

TLR signaling pathway. Ligand binding induces receptor dimerization and TLR interacts with TIR domain-containing adaptor proteins. (Left) TLR signaling occurs through a MYD88-dependent pathway. (Right) TLRs require other TIR domain-containing adaptors to induce cytokine expression, including TIRAP and TCAM. Purple ellipses denote conserved TIR domains. SOCS is a negative regulator of intracelluar cytokine signaling that can inhibit TLR responses.