{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:49:28Z","timestamp":1790794168621,"version":"4.1.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2018,8,1]],"date-time":"2018-08-01T00:00:00Z","timestamp":1533081600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Glucocorticoids (GCs) are commonly prescribed to patients with a variety of inflammatory disorders, including inflammatory bowel disease (IBD). GCs mediate their immunomodulatory effects through many different mechanisms and target multiple signaling pathways. The GC dexamethasone downmodulates innate and adaptive immune cell activation. IBD is the manifestation of a dysregulated immune response involving many different immune cells. Group 3 innate lymphocytes (ILC3s) have critical roles in mucosal inflammation. ILC3s secrete high levels of the cytokine IL-22, promoting epithelial proliferation, antimicrobial peptides, and mucins. In this study, we examined the effects of dexamethasone on IL-22 production by ILC3s. We found that dexamethasone suppressed IL-23\u2013mediated IL-22 production in human and mouse ILC3s. This was mediated in part through dexamethasone modulation of the NF-\u03baB pathway. Inhibition of NF-\u03baB signaling with a small molecule inhibitor also downmodulated IL-23\u2013 and IL-1\u03b2\u2013mediated IL-22 production in ILC3s. These findings implicate NF-\u03baB as a regulator of IL-22 in ILC3s and likely have repercussions on GC treatment of IBD patients.<\/jats:p>","DOI":"10.4049\/jimmunol.1800484","type":"journal-article","created":{"date-parts":[[2018,7,6]],"date-time":"2018-07-06T17:25:12Z","timestamp":1530897912000},"page":"1267-1274","source":"Crossref","is-referenced-by-count":17,"title":["Glucocorticoids Inhibit Group 3 Innate Lymphocyte IL-22 Production"],"prefix":"10.1093","volume":"201","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4910-8664","authenticated-orcid":false,"given":"Sudarshan","family":"Seshadri","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center , Oklahoma City, OK 73104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemary L","family":"Pope","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center , Oklahoma City, OK 73104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8787-5955","authenticated-orcid":false,"given":"Lauren A","family":"Zenewicz","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center , Oklahoma City, OK 73104"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,8,15]]},"reference":[{"key":"2025030417571785900_r1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/nrgastro.2015.186","article-title":"Immunopathogenesis of IBD: current state of the art","volume":"13","author":"de Souza","year":"2016","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"2025030417571785900_r2","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/nrgastro.2016.208","article-title":"Current and emerging therapeutic targets for IBD","volume":"14","author":"Neurath","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"2025030417571785900_r3","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nri3661","article-title":"Cytokines in inflammatory bowel disease","volume":"14","author":"Neurath","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"2025030417571785900_r4","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1053\/j.gastro.2005.06.071","article-title":"Interleukin-22, a member of the IL-10 subfamily, induces inflammatory responses in colonic subepithelial myofibroblasts","volume":"129","author":"Andoh","year":"2005","journal-title":"Gastroenterology"},{"key":"2025030417571785900_r5","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1002\/ibd.22929","article-title":"Healing of intestinal inflammation by IL-22","volume":"18","author":"Mizoguchi","year":"2012","journal-title":"Inflamm. Bowel Dis."},{"key":"2025030417571785900_r6","doi-asserted-by":"crossref","first-page":"5306","DOI":"10.4049\/jimmunol.1300016","article-title":"IL-22 deficiency alters colonic microbiota to be transmissible and colitogenic","volume":"190","author":"Zenewicz","year":"2013","journal-title":"J. Immunol."},{"key":"2025030417571785900_r7","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1084\/jem.20102149","article-title":"Memory\/effector (CD45RB(lo)) CD4 T cells are controlled directly by IL-10 and cause IL-22-dependent intestinal pathology","volume":"208","author":"Kamanaka","year":"2011","journal-title":"J. Exp. Med."},{"key":"2025030417571785900_r8","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/mi.2013.33","article-title":"IL-23R+ innate lymphoid cells induce colitis via interleukin-22-dependent mechanism","volume":"7","author":"Eken","year":"2014","journal-title":"Mucosal Immunol."},{"key":"2025030417571785900_r9","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/nrd4176","article-title":"Therapeutic opportunities of the IL-22-IL-22R1 system","volume":"13","author":"Sabat","year":"2014","journal-title":"Nat. Rev. Drug Discov."},{"key":"2025030417571785900_r10","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1146\/annurev-immunol-032414-112123","article-title":"Interleukin-22: immunobiology and pathology","volume":"33","author":"Dudakov","year":"2015","journal-title":"Annu. Rev. Immunol."},{"key":"2025030417571785900_r11","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/nature14189","article-title":"The biology of innate lymphoid cells","volume":"517","author":"Artis","year":"2015","journal-title":"Nature"},{"key":"2025030417571785900_r12","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/nm1720","article-title":"Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens","volume":"14","author":"Zheng","year":"2008","journal-title":"Nat. Med."},{"key":"2025030417571785900_r13","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.immuni.2008.11.003","article-title":"Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease","volume":"29","author":"Zenewicz","year":"2008","journal-title":"Immunity"},{"key":"2025030417571785900_r14","first-page":"534","article-title":"IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis","volume":"118","author":"Sugimoto","year":"2008","journal-title":"J. Clin. Invest."},{"key":"2025030417571785900_r15","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1084\/jem.20082683","article-title":"STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing","volume":"206","author":"Pickert","year":"2009","journal-title":"J. Exp. Med."},{"key":"2025030417571785900_r16","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.chom.2009.03.011","article-title":"Lipocalin-2 resistance confers an advantage to Salmonella enterica serotype Typhimurium for growth and survival in the inflamed intestine","volume":"5","author":"Raffatellu","year":"2009","journal-title":"Cell Host Microbe"},{"key":"2025030417571785900_r17","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.immuni.2011.11.011","article-title":"The aryl hydrocarbon receptor regulates gut immunity through modulation of innate lymphoid cells","volume":"36","author":"Qiu","year":"2012","journal-title":"Immunity"},{"key":"2025030417571785900_r18","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.immuni.2013.10.021","article-title":"Induction of innate lymphoid cell-derived interleukin-22 by the transcription factor STAT3 mediates protection against intestinal infection","volume":"40","author":"Guo","year":"2014","journal-title":"Immunity"},{"key":"2025030417571785900_r19","doi-asserted-by":"crossref","first-page":"ra45","DOI":"10.1126\/scisignal.aaf2223","article-title":"Notch signaling in group 3 innate lymphoid cells modulates their plasticity","volume":"9","author":"Chea","year":"2016","journal-title":"Sci. Signal."},{"key":"2025030417571785900_r20","doi-asserted-by":"crossref","first-page":"e1006690","DOI":"10.1371\/journal.ppat.1006690","article-title":"Bacillus anthracis lethal toxin negatively modulates ILC3 function through perturbation of IL-23-mediated MAPK signaling","volume":"13","author":"Seshadri","year":"2017","journal-title":"PLoS Pathog."},{"key":"2025030417571785900_r21","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/nri.2017.1","article-title":"Immune regulation by glucocorticoids","volume":"17","author":"Cain","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"2025030417571785900_r22","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1172\/JCI88886","article-title":"Glucocorticoid receptors: finding the middle ground","volume":"127","author":"Desmet","year":"2017","journal-title":"J. Clin. Invest."},{"key":"2025030417571785900_r23","doi-asserted-by":"crossref","first-page":"G218","DOI":"10.1152\/ajpgi.00095.2013","article-title":"Glucocorticoids regulate barrier function and claudin expression in intestinal epithelial cells via MKP-1","volume":"306","author":"Fischer","year":"2014","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"2025030417571785900_r24","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/mi.2014.71","article-title":"An in vitro model of innate lymphoid cell function and differentiation","volume":"8","author":"Allan","year":"2015","journal-title":"Mucosal Immunol."},{"key":"2025030417571785900_r25","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/0092-8674(92)90030-G","article-title":"RAG-1-deficient mice have no mature B and T lymphocytes","volume":"68","author":"Mombaerts","year":"1992","journal-title":"Cell"},{"key":"2025030417571785900_r26","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1002\/eji.1830240508","article-title":"Analysis of susceptibility of mature human T lymphocytes to dexamethasone-induced apoptosis","volume":"24","author":"Tuosto","year":"1994","journal-title":"Eur. J. Immunol."},{"key":"2025030417571785900_r27","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.clim.2014.09.007","article-title":"Increased ILC2s in the eosinophilic nasal polyp endotype are associated with corticosteroid responsiveness","volume":"155","author":"Walford","year":"2014","journal-title":"Clin. Immunol."},{"key":"2025030417571785900_r28","doi-asserted-by":"crossref","first-page":"11","DOI":"10.5402\/2012\/985495","article-title":"Applications of steroid in clinical practice: a review","volume":"2012","author":"Shaikh","year":"2012","journal-title":"ISRN Anesthesiol."},{"key":"2025030417571785900_r29","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/0014-4827(83)90282-3","article-title":"Inhibition of glucocorticosteroid action in cultured L-929 mouse fibroblasts by RU 486, a new anti-glucocorticosteroid of high affinity for the glucocorticosteroid receptor","volume":"147","author":"Jung-Testas","year":"1983","journal-title":"Exp. Cell Res."},{"key":"2025030417571785900_r30","doi-asserted-by":"crossref","first-page":"5699","DOI":"10.4049\/jimmunol.168.11.5699","article-title":"A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R","volume":"168","author":"Parham","year":"2002","journal-title":"J. Immunol."},{"key":"2025030417571785900_r31","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1111\/all.12840","article-title":"BCL-2 protects human and mouse Th17 cells from glucocorticoid-induced apoptosis","volume":"71","author":"Banuelos","year":"2016","journal-title":"Allergy"},{"key":"2025030417571785900_r32","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.cell.2016.12.012","article-title":"30 years of NF-\u03baB: a blossoming of relevance to human pathobiology","volume":"168","author":"Zhang","year":"2017","journal-title":"Cell"},{"key":"2025030417571785900_r33","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.cell.2008.01.020","article-title":"Shared principles in NF-kappaB signaling","volume":"132","author":"Hayden","year":"2008","journal-title":"Cell"},{"key":"2025030417571785900_r34","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.4049\/jimmunol.1601554","article-title":"IL-18 drives ILC3 proliferation and promotes IL-22 production via NF-\u03baB","volume":"199","author":"Victor","year":"2017","journal-title":"J. Immunol."},{"key":"2025030417571785900_r35","doi-asserted-by":"crossref","first-page":"21096","DOI":"10.1074\/jbc.272.34.21096","article-title":"Novel inhibitors of cytokine-induced IkappaBalpha phosphorylation and endothelial cell adhesion molecule expression show anti-inflammatory effects in vivo","volume":"272","author":"Pierce","year":"1997","journal-title":"J. Biol. Chem."},{"key":"2025030417571785900_r36","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.immuni.2010.12.009","article-title":"CD4(+) lymphoid tissue-inducer cells promote innate immunity in the gut","volume":"34","author":"Sonnenberg","year":"2011","journal-title":"Immunity"},{"key":"2025030417571785900_r37","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/nature11535","article-title":"IL-22BP is regulated by the inflammasome and modulates tumorigenesis in the intestine","volume":"491","author":"Huber","year":"2012","journal-title":"Nature"},{"key":"2025030417571785900_r38","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.immuni.2007.07.023","article-title":"Interleukin-22 but not interleukin-17 provides protection to hepatocytes during acute liver inflammation","volume":"27","author":"Zenewicz","year":"2007","journal-title":"Immunity"},{"key":"2025030417571785900_r39","doi-asserted-by":"crossref","first-page":"300ra128","DOI":"10.1126\/scitranslmed.aaa5657","article-title":"An inflammation-targeting hydrogel for local drug delivery in inflammatory bowel disease","volume":"7","author":"Zhang","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"2025030417571785900_r40","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.clim.2015.03.027","article-title":"Macromolecular glucocorticoid prodrug improves the treatment of dextran sulfate sodium-induced mice ulcerative colitis","volume":"160","author":"Ren","year":"2015","journal-title":"Clin. Immunol."},{"key":"2025030417571785900_r41","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.1038\/ajg.2010.140","article-title":"A prospective population-based study of triggers of symptomatic flares in IBD","volume":"105","author":"Bernstein","year":"2010","journal-title":"Am. J. Gastroenterol."},{"key":"2025030417571785900_r42","first-page":"E2960","article-title":"Chronic stress promotes colitis by disturbing the gut microbiota and triggering immune system response. [Published erratum appears in 2018 Proc. Natl. Acad. Sci. USA 115: E4542.]","volume":"115","author":"Gao","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/201\/4\/1267\/61871205\/ji1800484.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/201\/4\/1267\/61871205\/ji1800484.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T20:09:47Z","timestamp":1741118987000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/201\/4\/1267\/7953662"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8]]},"references-count":42,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,8,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1800484","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2018,8]]},"published":{"date-parts":[[2018,8]]}}}