Regulation of interleukin‐1β by interferon‐γ is species specific,limited by suppressor of cytokine signalling 1 and influences interleukin‐17 production |
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| Authors: | Ann L Cornish Caroline E Sutton Joanne O'Donnell Louise H Cengia Andrew W Roberts Ian P Wicks Kingston H G Mills Ben A Croker |
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| Affiliation: | 1. Autoimmunity and Transplantation Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria, 3052 Australia;2. Immune Regulation Research Group, School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland;3. Cancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria, 3052 Australia;4. Immunology Research Centre, School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland |
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| Abstract: | Reports describing the effect of interferon‐γ (IFNγ) on interleukin‐1β (IL‐1β) production are conflicting. We resolve this controversy by showing that IFNγ potentiates IL‐1β release from human cells, but transiently inhibits the production of IL‐1β from mouse cells. Release from this inhibition is dependent on suppressor of cytokine signalling 1. IL‐1β and Th17 cells are pathogenic in mouse models for autoimmune disease, which use Mycobacterium tuberculosis (MTB), in which IFNγ and IFNβ are anti‐inflammatory. We observed that these cytokines suppress IL‐1β production in response to MTB, resulting in a reduced number of IL‐17‐producing cells. In human cells, IFNγ increased IL‐1β production, and this might explain why IFNγ is detrimental for multiple sclerosis. In mice, IFNγ decreased IL‐1β and subsequently IL‐17, indicating that the adaptive immune response can provide a systemic, but transient, signal to limit inflammation. |
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| Keywords: | IFNγ IL‐17 IL‐1β inflammasome SOCS1 |
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