Loss of immune tolerance to IL-2 in type 1 diabetes.
Louis PérolJohn M LindnerPamela CaudanaNicolas Gonzalo NunezAudrey BaeyensAndrea ValleChristine SedlikDelphine LoiratOlivier BoyerAlain CréangeJosé Laurent CohenUte Christine RognerJun YamanouchiMartine MarchantXavier Charles LeberMeike ScharenbergMarie-Claude GagneraultRoberto MalloneManuela BattagliaPere SantamariaAgnès HartemannElisabetta TraggiaiEliane PiaggioPublished in: Nature communications (2016)
Type 1 diabetes (T1D) is characterized by a chronic, progressive autoimmune attack against pancreas-specific antigens, effecting the destruction of insulin-producing β-cells. Here we show interleukin-2 (IL-2) is a non-pancreatic autoimmune target in T1D. Anti-IL-2 autoantibodies, as well as T cells specific for a single orthologous epitope of IL-2, are present in the peripheral blood of non-obese diabetic (NOD) mice and patients with T1D. In NOD mice, the generation of anti-IL-2 autoantibodies is genetically determined and their titre increases with age and disease onset. In T1D patients, circulating IgG memory B cells specific for IL-2 or insulin are present at similar frequencies. Anti-IL-2 autoantibodies cloned from T1D patients demonstrate clonality, a high degree of somatic hypermutation and nanomolar affinities, indicating a germinal centre origin and underscoring the synergy between cognate autoreactive T and B cells leading to defective immune tolerance.
Keyphrases
- type diabetes
- end stage renal disease
- multiple sclerosis
- newly diagnosed
- ejection fraction
- glycemic control
- systemic lupus erythematosus
- peripheral blood
- chronic kidney disease
- prognostic factors
- adipose tissue
- metabolic syndrome
- cell proliferation
- induced apoptosis
- cell death
- immune response
- signaling pathway
- obese patients
- bariatric surgery
- high fat diet induced
- weight loss
- genome wide
- dna methylation
- pi k akt
- cell cycle arrest
- wound healing