{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T03:30:19Z","timestamp":1791689419876,"version":"4.3.4"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T00:00:00Z","timestamp":1637020800000},"content-version":"vor","delay-in-days":397,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012041","name":"Versus Arthritis","doi-asserted-by":"publisher","award":["19437"],"award-info":[{"award-number":["19437"]}],"id":[{"id":"10.13039\/501100012041","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012041","name":"Versus Arthritis","doi-asserted-by":"publisher","award":["21430"],"award-info":[{"award-number":["21430"]}],"id":[{"id":"10.13039\/501100012041","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,13]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>Interferons (IFNs) are key regulators of a number of inflammatory conditions in which neutrophils play an important role in pathology, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), where type I IFNs are implicated in disease pathology. However, IFNs are usually generated in vivo together with other cytokines that also have immunoregulatory functions, but such interactions are poorly defined experimentally. We measured the effects of type I (IFN-\u03b1) IFN, elevated in both RA and SLE, on the functions of healthy neutrophils incubated in vitro in the absence and presence of proinflammatory cytokines typically elevated in inflammatory diseases [tumour necrosis factor (TNF-\u03b1), granulocyte\u2013macrophage colony-stimulating factor (GM-CSF)]. IFN-\u03b1 alone had no effect on neutrophil apoptosis; however, it abrogated the anti-apoptotic effect of GM-CSF (18\u00a0h, P\u00a0&amp;lt;\u00a00\u00b701). The enhanced stability of the anti-apoptotic protein myeloid cell leukaemia 1 (Mcl-1) and delayed activation of caspase activation normally regulated by GM-CSF were blocked by IFN-\u03b1: this effect was mediated, in part, by activation of p38 mitogen-activated protein kinase (MAPK). IFN-\u03b1 alone also primed reactive oxygen species (ROS) production and maintained the transient priming effect of TNF-\u03b1 for up to 4\u00a0h: it also down-regulated GM-CSF- and TNF-\u03b1-activated expression of chemokine (C-X-C motif) ligand (CXCL)1, CXCL2, CXCL3, CXCL8, CCL3 and CCL4 but, in contrast, increased the expression of CXCL10. These novel data identify complex regulatory signalling networks in which type I IFNs profoundly alter the response of neutrophils to inflammatory cytokines. This is likely to have important consequences in vivo and may explain the complexity and heterogeneity of inflammatory diseases such as RA, in which multiple cytokine cascades have been activated.<\/jats:p>","DOI":"10.1111\/cei.13525","type":"journal-article","created":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T07:34:07Z","timestamp":1601364847000},"page":"151-159","source":"Crossref","is-referenced-by-count":51,"title":["Type I interferon regulates cytokine-delayed neutrophil apoptosis, reactive oxygen species production and chemokine expression"],"prefix":"10.1093","volume":"203","author":[{"given":"L","family":"Glennon-Alty","sequence":"first","affiliation":[{"name":"Institute of Life Course and Medical Sciences, University of Liverpool , Liverpool, Merseyside, UK"},{"name":"Liverpool Health Partners, University of Liverpool , Liverpool, Merseyside, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7019-6211","authenticated-orcid":false,"given":"R J","family":"Moots","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Aintree University Hospital , Liverpool, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S W","family":"Edwards","sequence":"additional","affiliation":[{"name":"Institute of Infection, Veterinary and Ecological Science, University of Liverpool , Liverpool, Merseyside, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0442-3134","authenticated-orcid":false,"given":"H L","family":"Wright","sequence":"additional","affiliation":[{"name":"Institute of Life Course and Medical Sciences, University of Liverpool , Liverpool, Merseyside, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,10,15]]},"reference":[{"key":"2023081113341099900_cei13525-bib-0001","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/nri1604","article-title":"Mechanisms of type-I- and type-II-interferon-mediated signalling","volume":"5","author":"Platanias","year":"2005","journal-title":"Nat Rev Immunol"},{"key":"2023081113341099900_cei13525-bib-0002","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1189\/jlb.1208761","article-title":"Interferon-lambdas: the modulators of antivirus, antitumor, and immune responses","volume":"86","author":"Li","year":"2009","journal-title":"J Leukoc Biol"},{"key":"2023081113341099900_cei13525-bib-0003","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.immuni.2012.03.014","article-title":"JAK and STAT signaling molecules in immunoregulation and immune-mediated 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