VIP is a Serious and Powerful Controller of
Inflammation and Autoimmunity
A massive and major inflammation control chemical is VIP:
Vasoactive intestinal peptide induces regulatory T cells during experimental autoimmune encephalomyelitis.
CD4(+)CD25(+) regulatory T cells (Treg) control the immune response to a variety of antigens, including self-antigens. Several models support the idea of the peripheral generation of CD4(+)CD25(+) Treg from CD4(+)CD25(-) T cells. Little is known about the endogenous factors and mechanisms controlling the peripheral expansion of CD4(+)CD25(+) Treg. In this study we report on the capacity of the vasoactive intestinal peptide (VIP), an immunosuppressive neuropeptide, to induce functional Treg in vivo during the development of experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis model. The administration of VIP to EAE mice results in the expansion of the CD4(+)CD25(+), Foxp3-expressing T cells in the periphery and the nervous system, which inhibit encephalitogenic T cell activation. In addition to the increase in the number of CD4(+)CD25(+) Treg, VIP induces more efficient suppressors on a per cell basis. The VIP-generated CD4(+)CD25(+) Treg transfer suppression and significantly ameliorate the progression of the disease.
Fernandez-Martin A, Gonzalez-Rey E, Chorny A, Ganea D, Delgado M. Eur J Immunol. 2006 Jan 10
Vasoactive intestinal peptide generates human tolerogenic dendritic cells that induce CD4 and CD8 regulatory T cells.
Induction of antigen-specific tolerance is critical for autoimmunity prevention and immune tolerance maintenance. In addition to their classical role as sentinels of the immune response, dendritic cells (DCs) play important roles in maintaining peripheral tolerance through the induction/activation of regulatory T cells (Tr). The possibility to generate tolerogenic DCs opens new therapeutic perspectives in autoimmune/inflammatory diseases. The characterization of endogenous factors that contribute to the development of tolerogenic DCs is highly relevant. We here report that the immunosuppressive neuropeptide, vasoactive intestinal peptide (VIP), induces the generation of human tolerogenic DCs with the capacity to generate CD4 and CD8 Tr from their respective naive subsets. The presence of VIP during the early stages of DC differentiation from blood monocytes generates a population of IL-10-producing DCs unable to fully mature following inflammatory stimuli. CD4 Tr generated with VIP-differentiated DCs resemble the previously described Tr1 in terms of phenotype and cytokine profile. CD8 Tr generated with tolerogenic VIP-DCs have increased numbers of IL-10-producing CD8(+)CD28(-)CTLA4(+) T cells. Both CD4 and CD8 Tr suppress primarily antigen-specific Th1-mediated responses. Therefore, the possibility to generate/expand ex vivo tolerogenic DCVIP opens new therapeutic perspectives for the treatment of autoimmune diseases and allogeneic transplantation in humans.
Gonzalez-Rey E, Chorny A, Fernandez-Martin A, Ganea D, Delgado M. Blood. 2006 Jan 5
[Underlined, colored and bolded text from Dr. Schaller's insertions]