title: Altered immune regulation in type 1 diabetes.
abstract: Research in genetics and immunology was going on separate strands for a long time. Type 1 diabetes mellitus might not be characterized with a single pathogenetic factor. It develops when a susceptible individual is exposed to potential triggers in a given sequence and timeframe that eventually disarranges the fine-tuned immune mechanisms that keep autoimmunity under control in health. Genomewide association studies have helped to understand the congenital susceptibility, and hand-in-hand with the immunological research novel paths of immune dysregulation were described in central tolerance, apoptotic pathways, or peripheral tolerance mediated by regulatory T-cells. Epigenetic factors are contributing to the immune dysregulation. The interplay between genetic susceptibility and potential triggers is likely to play a role at a very early age and gradually results in the loss of balanced autotolerance and subsequently in the development of the clinical disease. Genetic susceptibility, the impaired elimination of apoptotic β -cell remnants, altered immune regulatory functions, and environmental factors such as viral infections determine the outcome. Autoreactivity might exist under physiologic conditions and when the integrity of the complex regulatory process is damaged the disease might develop. We summarized the immune regulatory mechanisms that might have a crucial role in disease pathology and development.
authors.affiliation: Second Department of Medicine, Semmelweis University, Szentkirályi Street 46, Budapest 1088, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Zóka
authors.forename: Györgyi
authors.initials: G
authors.lastname: Műzes
authors.forename: Anikó
authors.initials: A
authors.lastname: Somogyi
authors.forename: Tímea
authors.initials: T
authors.lastname: Varga
authors.forename: Barbara
authors.initials: B
authors.lastname: Szémán
authors.forename: Zahra
authors.initials: Z
authors.lastname: Al-Aissa
authors.forename: Orsolya
authors.initials: O
authors.lastname: Hadarits
authors.forename: Gábor
authors.initials: G
authors.lastname: Firneisz
mesh_terms: D000818:Animals; D017209:Apoptosis; D015551:Autoimmunity / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D004777:Environment; D044127:Epigenesis, Genetic; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics; D012307:Risk Factors