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Engineered Gut Bacteria Reverse Type 1 Diabetes in Experimental Mice

Scientists have managed to reverse type 1 diabetes (T1D) in experimental mice by giving the animals an oral course of harmless gut bacteria that had been engineered to secrete the whole proinsulin autoantigen (PINS) and the immunomodulatory human cytokine IL-10 (hIL10). An international team led by scientists at the KU Leuven in Belgium, combined the engineered Lactococcus lactis therapy with a short, low-dose systemic course of the nonspecific immune modulating monoclonal antibody (mAb) anti-CD3.

Treated non-obese diabetic (NOD) mice demonstrated stable levels of glycemia for over three months of follow-up, and suppression of diabetes-related autoantigen immune responses specifically, without any effect on their immune responses to nondisease antigens. The stable reversal of established diabetes in animals given the combination treatment was accompanied by increased numbers of local antigen-specific Foxp3+ regulatory T cells (Tregs) that accumulated in pancreatic islets.

Chantal Mathieu, M.D., and colleagues claim their findings suggest the same approach could be harnessed as an effective treatment for T1D in humans. The researchers describe their technique and report on their in vivo experiments in the Journal of Clinical Investigation in a paper titled “Reversal of autoimmune diabetes by restoration of antigen-specific tolerance using genetically modified Lactococcus lactis in mice.”
 
 

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