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Summary of the biology of IL-12

The main physiological producers of interleukin-12 (IL-12) are phagocytes (monocytes/macrophages and neutrophils) and dendritic Cell s in response to pathogens (bacteria, fungi, intracellular parasites and viruses) through Toll-like receptors (TLRs) and other receptors, to membrane-bound and soluble signals from activated T cells and natural killer (NK) cells, and to components of the inflammatory extracellular matrix (for example, low-molecular-weight hyaluronan) through CD44 and TLRs. The physiologically most important target cells of IL-12 are: haematopoietic progenitors, for which, in synergy with other colony-stimulating factors, IL-12 induces increased proliferation and colony formation; NK cells, NKT cells and T cells, for which IL-12 induces proliferation, enhancement of cytotoxicity and of the expression of cytotoxic mediators, and the production of cytokines, particularly interferon-γ (IFN-γ ), as well as favouring differentiation to Cell s that produce type-1 cytokines (TH1, TC1 and NK1 cells); and B cells, for which IL-12, directly or through the effects of type-1 cytokines such as IFN-γ , enhances the activation and production of TH1-associated classes of immunoglobulin (for example, IgG2a in the mouse). CTL, cytotoxic T lymphocyte; GM-CSF, granulocyte–macrophage colony-stimulating factor; RANKL, receptor activator of nuclear factor-κ B ligand; SCF, stem-Cell factor; TC1, T cytotoxic 1; TH1, T helper 1; TNF, tumour-necrosis factor.