Cobitolimod induces anti-inflammatory effects by balancing Th17/T-reg cell response

Cobitolimod – a DNA-based oligonucleotide which is a toll-like receptor 9 agonist – can modulate the immune system in UC by balancing the mucosal Th17/T-reg cell response. Cobitolimod decreases IL-17 expression and the number of Th17 cells, while increasing mucosal IL-10 expression and the quantity of T-reg cells.

This was shown by incubating isolated peripheral blood or mucosal immune cells from UC patients with cobitolimod in vitro. It emerged that after incubation these cells demonstrated significantly decreased IL-17 and increased IL-10 expression in comparison with cells from controls.

A quantitative immunohistochemical analysis was made of colon biopsies from UC patients taken before and four weeks after local cobitolimod treatment. It clearly indicated a significant induction of IL-10+ and a pronounced reduction of IL-17+ mucosal immune cells, which was not observed in the placebo group. In addition, FOXP3+ T-reg cells were significantly increased in the colon of UC patients upon cobitolimod treatment.

The researchers concluded that local administration of the toll-like receptor 9 agonist cobitolimod modulates the Th17/T-reg imbalance in mucosal inflammation. These findings indicate that cobitolimod addresses new therapeutic targets in the immunopathogenesis of UC, leading to pronounced anti-inflammatory effects [8].