Control of immune tolerance by vasoactive intestinal peptide (WP4484)

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.

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