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IL-2 fragments produced after cleavage by MMP-9 remained linked by a disulfide bond and displayed a reduced affinity for all IL-2 receptor subunits and a distinct pattern and timing of signal transduction. Stimulation of IL-2-dependent cells, including murine CTLL-2 and primary human regulatory T cells, with cleaved IL-2 resulted in significantly decreased proliferation. The concerted action of neutrophil proteases destroyed IL-2. Our data suggest that in neutrophil-rich inflammatory conditions in vivo, neutrophil MMP-9 may reduce the abundance of signaling-competent IL-2 and generate a fragment that competes with IL-2 for receptor binding, whereas the combined activity of granulocyte proteases has the potential to degrade and thus eliminate bioavailable IL-2.<\/jats:p>","DOI":"10.1042\/bcj20180382","type":"journal-article","created":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T20:15:37Z","timestamp":1562012137000},"page":"2191-2208","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Gelatinase B\/matrix metalloproteinase-9 and other neutrophil proteases switch off interleukin-2 activity"],"prefix":"10.1042","volume":"476","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5093-1757","authenticated-orcid":false,"given":"Vasily","family":"Rybakin","sequence":"first","affiliation":[{"name":"Laboratory of Immunobiology, Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven, Herestraat 49\/1030, Leuven 3000, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Stas","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology, Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven, Herestraat 49\/1030, Leuven 3000, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estefania","family":"Ugarte-Berzal","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology, Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven, Herestraat 49\/1030, Leuven 3000, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Noppen","sequence":"additional","affiliation":[{"name":"Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven, Herestraat 49\/1044, Leuven 3000, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7157-3370","authenticated-orcid":false,"given":"Jennifer","family":"Vandooren","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology, Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven, Herestraat 49\/1030, Leuven 3000, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilse","family":"Van Aelst","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology, Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven, Herestraat 49\/1030, Leuven 3000, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Liekens","sequence":"additional","affiliation":[{"name":"Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven, Herestraat 49\/1044, Leuven 3000, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Proost","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven, Herestraat 49\/1042, Leuven 3000, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5182-6361","authenticated-orcid":false,"given":"Ghislain","family":"Opdenakker","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology, Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven, Herestraat 49\/1030, Leuven 3000, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2019,8,9]]},"reference":[{"key":"2021112217592973300_BCJ-2018-0382C1","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1126\/science.1260044","article-title":"T cell signaling. antigen affinity, costimulation, and cytokine inputs sum linearly to amplify T cell expansion","volume":"346","year":"2014","journal-title":"Science"},{"key":"2021112217592973300_BCJ-2018-0382C2","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1016\/j.coi.2010.02.013","article-title":"Inflammatory cytokines as a third signal for T cell activation","volume":"22","year":"2010","journal-title":"Curr. 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