New insights into the role of VIP on the ratio of T‐cell subsets during the development of autoimmune diabetes

Type I diabetes is an autoimmune T‐cell‐mediated disease associated with overexpression of inflammatory mediators and the disturbance of different T‐cell subsets. Vasoactive intestinal peptide (VIP) is a potent anti‐inflammatory agent with regulatory effects on activated T cells. As the equilibrium between different T‐cell subsets is involved in the final outcome, leading to tolerance or autoimmunity, we studied the evolution of markers for T cells in nonobese diabetic (NOD) mice. The study of different transcription factors, cytokines or cytokine receptors, shows that VIP interferes with functional phase of T helper 17 (Th17) cells and prevents the increase in the proportion of Th1 to Th17 cells. On the other hand, VIP‐treated NOD mice show an increase in the proportion of CD4 + CD25 + cells in the spleen. Thus, VIP switches the Tregs/Th17 ratio leading to tolerance in NOD mice. Similarly, VIP reverses the ratio of Th1‐/Th2‐cell subsets associated with autoimmune pathology. All these effects on the ratio of T‐cell subsets and the anti‐inflammatory effect of VIP in decreasing proinflammatory mediators result in a reduction of β‐cell destruction in pancreas. Taken together, these results show that VIP provides significant protection against spontaneous diabetes by modulating T‐cell subsets and counterbalancing tolerance and immunity.