&NA; The metabolic syndrome has been demonstrated in gene deficient animals, e.g. db/db mice, to include a systemic inflammation leading to insulin resistance, obesity and type 2 diabetes (T2D). To… Click to show full abstract
&NA; The metabolic syndrome has been demonstrated in gene deficient animals, e.g. db/db mice, to include a systemic inflammation leading to insulin resistance, obesity and type 2 diabetes (T2D). To determine the importance of inflammation in obesity and diabetes, in a normal non‐genetically modified species, an intervention study with neutralizing anti‐IL‐20 antibodies was conducted in the spontaneous T2D model Psammomys obesus. All IL‐20 receptor chains were expressed on protein level in the Psammomys obesus. Neutralization of IL‐20 did not modulate blood glucose, HbA1c, insulin levels or lymphocyte numbers after five weeks treatment although a trend to reduced weight gain rate was observed upon anti‐IL‐20 treatment. Inhibition of IL‐20 significantly increased the number of CD11bhigh/low cells and the CD11bGr‐1int myeloid derived suppressor cells in the spleen. Importantly, although the number of M1‐like monocytes remained unchanged the M1‐like marker CD11c expression level was reduced on the cells upon anti‐IL‐20 treatment. Anti‐IL‐20 treatment reduced both TLR4 and CCR2b expression on the macrophages upon treatment. Further, a marked shift in the protein signature in the pancreatic tissue after anti‐IL‐20 treatment was observed including enhanced expression of CXCL12, TIMP‐1 and IL‐10 while IL‐1&bgr;, CXCL4, PEDF and ADAMTS1 were reduced. In conclusion, we describe for the first time the systemic immune response in the diabetic Psammomys obesus. Neutralizing IL‐20 modulated the myeloid compartment, the adaptive immunity, and local expression of proteins in the diabetic pancreatic tissue as well as improved on weight gain and hence may place IL‐20 as a cytokine to be considered in obesity. HighlightsMethod and material to evaluate immunity in Psammomys obesus is provided.IL‐20 contribute to low‐grade pro‐inflammation e.g. polarization of M1 macrophages.Systemic inhibition of IL‐20 increase the myeloid derived suppressor cells.Neutralization of IL‐20 partly reduce weight gain.
               
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