Protective role of adenovirus vector-mediated interleukin-10 gene therapy on endogenous islet β-cells in recent-onset type 1 diabetes in NOD mice

Abstract

Abstract. The aim of the present study was to provide an animal experimental basis for the protective effect of the adenoviral vector-mediated interleukin-10 (Ad-mIL-10) gene on islet β-cells during the early stages of type 1 diabetes (T1D) in non-obese diabetic (NOD) mice. A total of 24 female NOD mice at the onset of diabetes were allocated at random into three groups (n=8 per group): Group 1, intraperitoneally injected with 0

Cytokines in type 1 diabetes: mechanisms of action and immunotherapeutic targets

“…Several therapeutic interventions that activate IL-10 have been reported to improve b-cell function, inhibit insulitis progression, and prevent the occurrence of diabetes in animal models. 35,36 The protective effects of IL-10 have also been reported in humans, as suggested by a strong correlation between increased IL-10 expression and disease attenuation. 37,38 The mechanisms proposed for the regulation of T1D by IL-10 involve increases in Treg frequencies and Th2-type cytokine (IL-4 and IL-10) levels, as well as the suppression of Th1-type cytokines (IL-2 and IFN-c) ( Figure 1 and Table 1).…”

“…Several therapeutic interventions that activate IL‐10 have been reported to improve β‐cell function, inhibit insulitis progression, and prevent the occurrence of diabetes in animal models . The protective effects of IL‐10 have also been reported in humans, as suggested by a strong correlation between increased IL‐10 expression and disease attenuation .…”

“…115 These data suggest that the protective effect of islet IL-35 is independent of the induction/expansion of pancreas-resident immunosuppressive T cells. However, after systemic treatment of established diabetes with an IL-35 recombinant protein, IL-35 promoted a phenotypic shift of Tregs, which resulted in an increase in anti-inflammatory (IL-10, IL- 35 and TGF-b) and a decrease in proinflammatory (IFN-c, IL-2 and IL-17) cytokines, counteracting the autoimmune attack in T1D. 116 This effect is partly attributed to the induction of Eos expression and IL-35 production in Tregs (Figure 1).…”

Type-I interferons inhibit interleukin-10 signaling and favor type 1 diabetes development in NOD mice

“…Targeting IL-10 signaling has already been considered in the treatment of this disease [16, 17]. However, inconsistent effects have been reported [45–48]. Based on our results, we suggest that, rather than augmenting the concentration of IL-10, a targeted restoration of the IL-10 impact on diabetogenic cells (via a timed and localized intervention) would achieve more successful therapeutic outcomes.…”

Unique Features of Pancreatic-Resident Regulatory T Cells in Autoimmune Type 1 Diabetes

“…In addition to TGF-β, IL-10 expression was also found in subsets of pancreatic-resident Tregs ( 27 ). IL-10, as an important immunomodulatory cytokine, is described to reduce IFN-γ in pancreatic β cells and prevent diabetes progression ( 42 ). IL-10 further promoted differentiation of IL-10-secreting Tregs, which formed a positive regulatory loop in IL-10 production and IL-10 + Treg induction ( 43 ).…”