{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T22:19:44Z","timestamp":1793225984882,"version":"4.5.0"},"reference-count":49,"publisher":"American Society for Clinical Investigation","issue":"3","funder":[{"name":"NIH and American Asthma Foundation","award":["R01NS071996,P01 CA062220-21 project 3,P01 HL103453 project 2,18-LIXI-EX1"],"award-info":[{"award-number":["R01NS071996,P01 CA062220-21 project 3,P01 HL103453 project 2,18-LIXI-EX1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,2,13]]},"abstract":"<jats:p>\n                    IL-17A plays a critical role in the pathogenesis of steroid-resistant neutrophilic airway inflammation, which is a hallmark of severe asthma and chronic obstructive pulmonary disease (COPD). Through RNA sequencing analysis of transcriptomes of human airway smooth muscle cells treated with IL-17A, dexamethasone (DEX, a synthetic glucocorticoid drug), alone or in combination, we identified a group of genes that are synergistically induced by IL-17A and DEX, including the neutrophil-promoting cytokine\n                    <jats:italic>CSF3<\/jats:italic>\n                    . In type-17 (Th17\/IL-17A\n                    <jats:sup>hi<\/jats:sup>\n                    ) preclinical models of neutrophilic severe asthma (acute and chronic) and COPD, although DEX treatment was able to reduce the expression of neutrophil-mobilizing\n                    <jats:italic>CXCL1<\/jats:italic>\n                    and\n                    <jats:italic>CXCL2<\/jats:italic>\n                    in lung tissue,\n                    <jats:italic>CSF3<\/jats:italic>\n                    expression was upregulated by DEX treatment. We found that DEX treatment alone failed to alleviate neutrophilic airway inflammation and pathology, and even exacerbated the disease phenotype when\n                    <jats:italic>CSF3<\/jats:italic>\n                    was highly induced. Disruption of the IL-17A\/DEX synergy by IL-17A inhibition with anti\u2013IL-17A mAb or cyanidin-3-glucoside (C3G, a small-molecule IL-17A blocker) or depletion of CSF3 effectively rendered DEX sensitivity in type-17 preclinical models of neutrophilic airway diseases. Our study elucidates what we believe is a novel mechanism of steroid resistance in type-17 neutrophilic airway inflammation and offers an effective steroid-sparing therapeutic strategy (combined low-dose DEX and C3G) for treating neutrophilic airway diseases.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.132836","type":"journal-article","created":{"date-parts":[[2020,2,12]],"date-time":"2020-02-12T16:11:52Z","timestamp":1581523912000},"source":"Crossref","is-referenced-by-count":63,"title":["Targeting IL-17A\/glucocorticoid synergy to CSF3 expression in neutrophilic airway 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