title: Caspase-1-processed IL-1 family cytokines play a vital role in driving innate IL-17.
abstract: The interleukin (IL)-1 cyokine family plays a vital role in inflammatory responses during infection and in autoimmune diseases. The pro-inflammatory cytokines, IL-1β and IL-18 are members of the IL-1 family that require cleavage by caspase-1 in the inflammasome to generate the mature active cytokines. Cells of the innate immune system, including γδ T cells and invariant natural killer T (iNKT) cells respond rapidly to invading pathogens by producing inflammatory cytokines, such as IFN-γ and IL-17. IL-1β or IL-18 in combination with IL-23 can induce IL-17 production by γδ T cells without T cell receptor (TCR) engagement. IL-1β and IL-23 can also synergize to induce IL-17 production by iNKT cells. Furthermore, CD4+ αβ effector memory T cells secrete IL-17 in response to IL-23 in combination with either IL-1β or IL-18, in the absence of any TCR stimulation. The early IL-17 produced by innate cells induces recruitment of neutrophils to the site of infection, stimulates local epithelial cells to secrete anti-microbial proteins, such as lipocalins and calgranulins, induces production of structural proteins important in tight junction stability, and promotes production of matrix metalloproteinases. Caspase-1 processed IL-1 family cytokines therefore play a vital role in the innate immune response and induction of IL-17 from innate immune cells which functions to fight infections and promote autoimmunity.
authors.affiliation: School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland.
authors.forename: Lara S
authors.initials: LS
authors.lastname: Dungan
authors.forename: Kingston H G
authors.initials: KH
authors.lastname: Mills
mesh_terms: D000818:Animals; D020170:Caspase 1 / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007375:Interleukin-1 / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology*; D011499:Protein Processing, Post-Translational / Q000276:immunology*; D017472:Receptors, Interleukin-1 / Q000276:immunology
chemical_list: D007375:Interleukin-1; D020381:Interleukin-17; D017472:Receptors, Interleukin-1; D020170:Caspase 1