title: Gene/environment interactions in the pathogenesis of autoimmunity: new insights on the role of Toll-like receptors.
abstract: Autoimmune disorders are increasing worldwide. Although their pathogenesis has not been elucidated yet, a complex interaction of genetic and environmental factors is involved in their onset. Toll-like receptors (TLRs) represent a family of pattern recognition receptors involved in the recognition and in the defense of the host from invading microorganisms. They sense a wide range of pathogen associated molecular patterns (PAMPs) deriving from metabolic pathways selective of bacterial, viral, fungal and protozoan microorganisms. TLR activation plays a critical role in the activation of the downstream signaling pathway by interacting and recruiting several adaptor molecules. Although TLRs are involved in the protection of the host, several studies suggest that, in certain conditions, they play a critical role in the pathogenesis of autoimmune diseases. We review the most recent advances showing a correlation between some single nucleotide polymorphisms or copy number variations in TLR genes or in adaptor molecules involved in TLR signaling and the onset of several autoimmune conditions, such as Type I diabetes, autoimmune polyendocrinopathy candidiasis-ectodermal dystrophy, rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis. In light of the foregoing we finally propose that molecules involved in TLR pathway may represent the targets for novel therapeutic treatments in order to stop autoimmune processes.
authors.affiliation: Immunology and Pharmacotherapy Area, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy; Vismederi Srl, Siena, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Gianchecchi
authors.affiliation: Immunology and Pharmacotherapy Area, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy. Electronic address: alessandra.fierabracci@opbg.net.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fierabracci
mesh_terms: D000818:Animals; D015551:Autoimmunity; D056915:DNA Copy Number Variations; D059647:Gene-Environment Interaction; D006801:Humans; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology*
chemical_list: D053594:Myeloid Differentiation Factor 88; D051193:Toll-Like Receptors
keywords: Autoimmunity; Candidate autoimmune genes; Etiopathogenesis; Prevention–treatment; TLR signaling pathway; Toll-like receptors