Upregulation of <i>FOXO3</i> in New‐Onset Type 1 Diabetes Mellitus

Abstract

Forkhead box O (FOXO) transcription factors have been implicated in the development and differentiation of the immune cells. FOXO3 plays a crucial role in physiologic and pathologic immune response. FOXO3, cooperatively with FOXO1, control the development and function of Foxp3 + regulatory T cells (T reg ). Since the lack of T reg ‐mediated control has fundamental impact on type 1 diabetes mellitus (T1DM) development, we investigated FOXO3 expression in patients with T1DM. FOXO3 expression was estimated in peripheral blood mononuclear cells (PBMCs) from newly diagnosed T1DM pediatric patients ( n = 28) and age‐matched healthy donors ( n = 27) by reahavel‐time PCR and TaqMan gene expression assays. Expression analysis revealed significant upregulation of FOXO3 in T1DM ( P = 0.0005). Stratification of the T1DM group according to the presence of initial diabetic ketoacidosis (DKA) did not indicate differences in FOXO3 expression in patients with DKA compared to a mild T1DM onset ( P &gt; 0.05). In conclusion, overexpression of FOXO3 is correlated with the ongoing islet autoimmune destruction and might suggest a potential role for this gene in the pathogenesis of type 1 diabetes mellitus.