title: Inflammation and type one diabetes.
abstract: Type one diabetes (T1D) is a complex T cell-mediated autoimmune disease, the defining feature of which is the destruction of the insulin-secreting beta- (β)- cell. Both genetic and environmental factors combine to precipitate disease, and the outcome of the pathological process is dependent on multiple inter-related factors. In this review, the mechanisms behind the initiation and propagation of the autoimmune response are analysed, and the contribution of differing T-helper (T(h)) subsets--in particular T(h)1- and T(h)17-related cytokines--to the disease process are discussed. An argument is then synthesized that proposes that the β-cell's response to stress and inflammation is the critical determinant in predicting disease outcome and that, immunologically, a delicate balance exists between regulation and inflammation at the site of islet infiltration. Strategies for disease intervention, therefore, will not only require the induction of T-cell tolerance by tipping the balance towards regulation but will also need to contain approaches that result in the scavenging of inflammatory mediators, in order to facilitate repair. Ultimately, given that clinical diabetes presents late in the autoimmune process, strategies for β-cell regeneration must now be addressed. There is thus a requirement for an increased, collaborative effort between stem cell biologists and immunologists in order to tailor an optimal therapeutic strategy for the treatment of this debilitating disease.
authors.affiliation: Rheumatology Unit, University College London Institute of Child Health, London WC1N 1EH, UK. d.bending@ucl.ac.uk
authors.forename: David
authors.initials: D
authors.lastname: Bending
authors.forename: Paola
authors.initials: P
authors.lastname: Zaccone
authors.forename: Anne
authors.initials: A
authors.lastname: Cooke
mesh_terms: D017209:Apoptosis / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000276:immunology* / Q000378:metabolism; D018448:Models, Immunological; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines