Control of immune tolerance by vasoactive intestinal peptide (Homo sapiens)

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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 cells 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.