{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:50:32Z","timestamp":1791341432253,"version":"4.3.1"},"reference-count":34,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R37 HL079142"],"award-info":[{"award-number":["R37 HL079142"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"HHS | National Institutes of Health (NIH) | NIAID","award":["F30AI114146"],"award-info":[{"award-number":["F30AI114146"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Interleukin 22 (IL-22) is an IL-10-related cytokine produced by T helper 17 (Th17) cells and other immune cells that signals via IL-22 receptor alpha 1 (IL-22Ra1), which is expressed on epithelial tissues, as well as hepatocytes. IL-22 has been shown to have hepatoprotective effects that are mediated by signal transducer and activator of transcription 3 (STAT3) signaling. However, it is unclear whether IL-22 can directly regulate antimicrobial programs in the liver. To test this hypothesis, hepatocyte-specific IL-22Ra1 knockout (\n            <jats:italic>Il22Ra1<\/jats:italic>\n            <jats:sup>Hep\u2212\/\u2212<\/jats:sup>\n            ) and Stat3 knockout (\n            <jats:italic>Stat3<\/jats:italic>\n            <jats:sup>\n              <jats:italic>Hep<\/jats:italic>\n              \u2212\/\u2212\n            <\/jats:sup>\n            ) mice were generated and subjected to intra-abdominal infection with\n            <jats:named-content content-type=\"genus-species\">Klebsiella pneumoniae<\/jats:named-content>\n            , which results in liver injury and necrosis. We found that overexpression of IL-22 or therapeutic administration of recombinant IL-22 (rIL-22), given 2 h postinfection, significantly reduced the bacterial burden in both the liver and spleen. The antimicrobial activity of rIL-22 required hepatic\n            <jats:italic>Il22Ra1<\/jats:italic>\n            and\n            <jats:italic>Stat3<\/jats:italic>\n            . Serum from rIL-22-treated mice showed potent bacteriostatic activity against\n            <jats:named-content content-type=\"genus-species\">K. pneumoniae<\/jats:named-content>\n            , which was dependent on lipocalin 2 (LCN2). However,\n            <jats:italic>in vivo<\/jats:italic>\n            , rIL-22-induced antimicrobial activity was only partially reduced in LCN2-deficient mice. We found that rIL-22 also induced serum amyloid A2 (SAA2) and that SAA2 had anti-\n            <jats:named-content content-type=\"genus-species\">K. pneumoniae<\/jats:named-content>\n            bactericidal activity\n            <jats:italic>in vitro<\/jats:italic>\n            . These results demonstrate that IL-22, through IL-22Ra1 and STAT3 singling, can induce intrinsic antimicrobial activity in the liver, which is due in part to LCN2 and SAA2. Therefore, IL-22 may be a useful adjunct in treating hepatic and intra-abdominal infections.\n          <\/jats:p>","DOI":"10.1128\/iai.01268-15","type":"journal-article","created":{"date-parts":[[2016,1,5]],"date-time":"2016-01-05T01:58:15Z","timestamp":1451959095000},"page":"782-789","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":49,"title":["Therapeutic Role of Interleukin 22 in Experimental Intra-abdominal Klebsiella pneumoniae Infection in Mice"],"prefix":"10.1128","volume":"84","author":[{"given":"Mingquan","family":"Zheng","sequence":"first","affiliation":[{"name":"R. K. Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Horne","sequence":"additional","affiliation":[{"name":"R. K. Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy P.","family":"McAleer","sequence":"additional","affiliation":[{"name":"R. K. Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek","family":"Pociask","sequence":"additional","affiliation":[{"name":"Tulane University, School of Medicine, Section of Pulmonary Diseases Critical Care and Environmental Medicine, New Orleans, Louisiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor","family":"Eddens","sequence":"additional","affiliation":[{"name":"R. K. Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"},{"name":"University of Pittsburgh School of Medicine, Department of Immunology, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misty","family":"Good","sequence":"additional","affiliation":[{"name":"R. K. Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Gao","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay K.","family":"Kolls","sequence":"additional","affiliation":[{"name":"R. K. Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2015.05.001"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/apt.13172"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-011-1605-2"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2013.19.4.349"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-009-0448-1"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-020711-075053"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxf096"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2004.07.007"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204204200"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1710"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1720"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1222551"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.07.023"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1271\/bbb.110061"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23837"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2015.02.008"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24339"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0803282"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201403-0475LE"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-009-0188-x"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.12032"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27447"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1256999"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2025"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20120260"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13823"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12232"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1254009"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20184"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25744"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27629"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.05114-11"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/379040"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2010.127"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.01268-15","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.01268-15","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T10:23:13Z","timestamp":1646475793000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.01268-15"}},"subtitle":[],"editor":[{"given":"A. 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