Toll-like receptor 3 (TLR3) and the development of type 1 diabetes mellitus.
Type 1 diabetes mellitus (T1DM) is a chronic, progressive autoimmune disease characterized by metabolic decompensation often leading to dehydration and ketoacidosis. Viral agents seem to play an important role in triggering the autoimmune destruction that leads to the development of T1DM. Among several viral strains investigated so far, the enterovirus family has been consistently associated with the onset of T1DM in humans. One of the mediators of viral damage is the double-stranded RNA (dsRNA) generated during replication and transcription of viral RNA and DNA. The Toll-like receptor 3 (TLR3) gene codes for an endoplasmic receptor of the pattern-recognition receptors (PRRs) family that recognizes dsRNA, plays an important role in the innate immune response triggered by viral infection. Binding of dsRNA to the TLR3 triggers the release of proinflammatory cytokines, such as interferons, which exhibit potent antiviral action; thus, protecting uninfected cells and inducing apoptosis of infected ones. Therefore, the TLR3 gene is a good candidate for the development of T1DM. Within this context, the objective of the present review was to address the role of the TLR3 gene in the development of T1DM.
Endocrinology Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Taís Silveira
TS
Assmann
Endocrinology Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Letícia de Almeida
Lde A
Brondani
Endocrinology Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Ana Paula
AP
Bouças
UFRGS, Porto Alegre, RS, Brazil.
Luís Henrique
LH
Canani
Endocrinology Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Daisy
D
Crispim
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology / Q000821:virology; D004770:Enterovirus / Q000276:immunology / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D007249:Inflammation / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism; D012330:RNA, Double-Stranded / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D051196:Toll-Like Receptor 3 / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication / Q000235:genetics / Q000276:immunology
D016207:Cytokines; D012330:RNA, Double-Stranded; D051196:Toll-Like Receptor 3