Control of immune tolerance by vasoactive intestinal peptide (WP4484)

Homo sapiens

Control of immune tolerance by VIP controls immune homeostasis. Vasoactive intestinal peptide (VIP) is released from nerve terminals (nervous source) and blood (endocrine source), or produced by T helper 2 (TH2) cells or macrophages (immune source) in response to antigenic and inflammatory stimulation. VIP induces immune tolerance and inhibits the autoimmune response through different non-excluding mechanisms. First, it induces the generation and differentiation of TH2-cell functions and decrease TH1-cell functions through direct actions on differentiating T cells, or indirectly by regulating antigen presenting cell (APC) functions. As a consequence, the inflammatory and autoimmune responses are impaired, and the anti-helminthic and atopic responses are increased, because the infiltration and activation of neutrophils and macrophages by interferon-γ (IFNγ) and the production of complement-activating IgG2 antibodies are avoided. Second, VIP impairs the co-stimulatory activity of APCs on effector T cells, inhibiting subsequent clonal expansion. This avoids the inflammatory response and its cytotoxic effect against the target tissue. Third, VIP induces the generation of regulatory T cells that suppress the activation of autoreactive T cells by producing interleukin-10 (IL-10) and transforming growth factor-β (TGFβ). This effect contributes to the maintenance of an anti-inflammatory state and restores immune tolerance.


Laurent Winckers , Anders Riutta , Egon Willighagen , Kristina Hanspers , and Denise Slenter


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Homo sapiens



Pathway Ontology

homeostasis pathway signaling pathway pertinent to immunity


Label Type Compact URI Comment
CD95 GeneProduct ncbigene:355
IL12A GeneProduct ncbigene:3592
IL12B GeneProduct ncbigene:3592
IFNG GeneProduct ncbigene:3458
IL2 GeneProduct ncbigene:3558
IL4 GeneProduct ncbigene:3565
IL5 GeneProduct ncbigene:3567
IL10 GeneProduct ncbigene:3586
CTLA4 GeneProduct ncbigene:1493
TGFB GeneProduct ncbigene:7040
VIP GeneProduct ncbigene:7432
MHCII GeneProduct reactome:R-HSA-8951502
TCR GeneProduct ncbiprotein:AAA61095
CD80 GeneProduct ncbigene:941
CD86 GeneProduct ncbigene:942
CD28 GeneProduct ncbigene:940
IL10 GeneProduct ncbigene:3586
CD86 GeneProduct ncbigene:942


  1. Regulation of immune tolerance by anti-inflammatory neuropeptides. Gonzalez-Rey E, Chorny A, Delgado M. Nat Rev Immunol. 2007 Jan;7(1):52–63. PubMed Europe PMC Scholia