{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T02:51:48Z","timestamp":1783565508339,"version":"3.55.0"},"reference-count":41,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T00:00:00Z","timestamp":1662336000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["SFB54"],"award-info":[{"award-number":["SFB54"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Interleukin\u20104 (IL\u20104) and its receptors (IL\u20104R) promote the proliferation and polarization of macrophages. However, it is unknown if IL\u20104R also influences monocyte homeostasis and if steady state IL\u20104 levels are sufficient to affect monocytes. Employing full IL\u20104 receptor alpha knockout mice (IL\u20104R\u03b1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) and mice with a myeloid\u2010specific deletion of IL\u20104R\u03b1 (IL\u20104R\u03b1\n                    <jats:sup>f\/f<\/jats:sup>\n                    LysM\n                    <jats:sup>cre<\/jats:sup>\n                    ), we show that IL\u20104 acts as a homeostatic factor regulating circulating monocyte numbers. In the absence of IL\u20104R\u03b1, murine monocytes in blood were reduced by 50% without altering monocytopoiesis in the bone marrow. This reduction was accompanied by a decrease in monocyte\u2010derived inflammatory cytokines in the plasma. RNA sequencing analysis and immunohistochemical staining of splenic monocytes revealed changes in mRNA and protein levels of anti\u2010apoptotic factors including\n                    <jats:italic>BIRC6<\/jats:italic>\n                    in IL\u20104R\u03b1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    knockout animals. Furthermore, assessment of monocyte lifespan in vivo measuring BrdU\n                    <jats:sup>+<\/jats:sup>\n                    cells revealed that the lifespan of circulating monocytes was reduced by 55% in IL\u20104R\u03b1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, whereas subcutaneously applied IL\u20104 prolonged it by 75%. Treatment of human monocytes with IL\u20104 reduced the amount of dying monocytes in vitro. Furthermore, IL\u20104 stimulation reduced the phosphorylation of proteins involved in the apoptosis pathway, including the phosphorylation of the NF\u03baBp65 protein. In a cohort of human patients, serum IL\u20104 levels were significantly associated with monocyte counts. In a sterile peritonitis model, reduced monocyte counts resulted in an attenuated recruitment of monocytes upon inflammatory stimulation in IL\u20104R\u03b1\n                    <jats:sup>f\/f<\/jats:sup>\n                    LysM\n                    <jats:sup>cre<\/jats:sup>\n                    mice without changes in overall migratory function. Thus, we identified a homeostatic role of IL\u20104R\u03b1 in regulating the lifespan of monocytes in vivo.\n                  <\/jats:p>","DOI":"10.1096\/fj.202101672rr","type":"journal-article","created":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T10:37:54Z","timestamp":1662374274000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Interleukin\u20104 receptor alpha signaling regulates monocyte homeostasis"],"prefix":"10.1096","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6874-5349","authenticated-orcid":false,"given":"Patrick","family":"Haider","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine II Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia B.","family":"Kral\u2010Pointner","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine II Medical University of Vienna  Vienna Austria"},{"name":"Ludwig Boltzmann Institute for Cardiovascular Research  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Salzmann","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine II Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Moik","sequence":"additional","affiliation":[{"name":"Division of Haematology and Haemostaseology, Comprehensive Cancer Center, Department of Internal Medicine I Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Bleichert","sequence":"additional","affiliation":[{"name":"Division of Vascular Surgery, Department of General Surgery Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waltraud C.","family":"Schrottmaier","sequence":"additional","affiliation":[{"name":"Institute of Vascular Biology and Thrombosis Research Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Kaun","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine II Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira","family":"Brekalo","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine II Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B.","family":"Fischer","sequence":"additional","affiliation":[{"name":"Department of Blood Group Serology and Transfusion Medicine Medical University of Vienna  Vienna Austria"},{"name":"Department of Biomedical Research Danube University Krems  Krems Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter S.","family":"Speidl","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine II Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Hengstenberg","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine II Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno K.","family":"Podesser","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Cardiovascular Research  Vienna Austria"},{"name":"Center for Biomedical Research Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt","family":"Huber","sequence":"additional","affiliation":[{"name":"3rd Department of Medicine, Cardiology and Intensive Care Medicine Wilhelminenhospital  Vienna Austria"},{"name":"Medical Faculty Sigmund Freud University  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Pabinger","sequence":"additional","affiliation":[{"name":"Division of Haematology and Haemostaseology, Comprehensive Cancer Center, Department of Internal Medicine I Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Knapp","sequence":"additional","affiliation":[{"name":"Laboratory of Infection Biology, Department of Internal Medicine I Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Brombacher","sequence":"additional","affiliation":[{"name":"Institute of Infectious Disease and Molecular Medicine International Center for Genetic and Biotechnology Cape Town Component &amp; University of Cape Town  Cape Town South 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