{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:53:00Z","timestamp":1782280380150,"version":"3.54.5"},"posted":{"date-parts":[[2025,1,19]]},"group-title":"Immunology","reference-count":75,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,1,19]],"date-time":"2025-01-19T00:00:00Z","timestamp":1737244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"crossref","award":["U01 AI160664"],"award-info":[{"award-number":["U01 AI160664"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"crossref","award":["F31 AI 161962"],"award-info":[{"award-number":["F31 AI 161962"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"crossref","award":["S10 OD032305"],"award-info":[{"award-number":["S10 OD032305"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,6,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Many inflammatory stimuli can induce progenitor cells in the bone marrow to produce increased numbers of myeloid cells as part of the process of emergency myelopoiesis. These events are associated with trained immunity and have long-term impacts on hematopoietic stem and progenitor cell (HSPC) development but can also compromise their function. While many cytokines support emergency myelopoiesis, less is known about the mechanisms that temper these events. When mice that lack the cytokine IL-27 were infected with\n                  <jats:italic>Toxoplasma gondii<\/jats:italic>\n                  , there was enhanced generation of monocyte progenitors and increased numbers of inflammatory monocytes. In the bone marrow of infected mice there was increased production of IL-27 that localized with HSPCs and a survey of cytokine receptor expression highlighted that HSPCs were uniquely poised to respond to IL-27. Furthermore, the use of\n                  <jats:italic>in vitro<\/jats:italic>\n                  differentiation assays and mixed bone marrow chimeras revealed that HSPCs from IL-27 deficient mice are pre-disposed towards the monocyte lineage. Additional studies highlighted that after infection loss of the IL-27R resulted in reduced HSPC fitness that manifested as reduced proliferative responses and a decreased ability to reconstitute the hematopoietic system. Thus, the ability of IL-27 to act on HSPC provides a regulatory brake on differentiation to limit monocyte induction and preserve HSPC stemness.\n                <\/jats:p>","DOI":"10.1101\/2025.01.15.633135","type":"posted-content","created":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T04:00:29Z","timestamp":1737345629000},"source":"Crossref","is-referenced-by-count":1,"title":["IL-27 limits HSPC differentiation during infection and protects from stem cell exhaustion"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2224-5159","authenticated-orcid":false,"given":"Daniel L.","family":"Aldridge","sequence":"first","affiliation":[{"name":"University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary","family":"Lanzar","sequence":"additional","affiliation":[{"name":"University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony T.","family":"Phan","sequence":"additional","affiliation":[{"name":"University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Christian","sequence":"additional","affiliation":[{"name":"University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Pardy","sequence":"additional","affiliation":[{"name":"University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Booki","family":"Min","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Feinber School of Medicine, Northwestern University, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9065-7895","authenticated-orcid":false,"given":"Ross M.","family":"Kedl","sequence":"additional","affiliation":[{"name":"University of Colorado, Anschuitz Medical Campus, Aurora, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3092-1428","authenticated-orcid":false,"given":"Christopher A.","family":"Hunter","sequence":"additional","affiliation":[{"name":"University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041209582275000_2025.01.15.633135v2.1","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.00083-24"},{"key":"2026041209582275000_2025.01.15.633135v2.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.05.011"},{"key":"2026041209582275000_2025.01.15.633135v2.3","doi-asserted-by":"crossref","unstructured":"Au - Amend, S.R. , K.C. Au - Valkenburg , and K.J. Au - Pienta . 2016. Murine Hind Limb Long Bone Dissection and Bone Marrow Isolation. JoVE e53936.","DOI":"10.3791\/53936-v"},{"key":"2026041209582275000_2025.01.15.633135v2.4","first-page":"D917","article-title":"BloodSpot: a database of gene expression profiles and transcriptional programs for healthy and malignant haematopoiesis","volume":"44","year":"2015","journal-title":"Nucleic Acids Research"},{"key":"2026041209582275000_2025.01.15.633135v2.5","doi-asserted-by":"publisher","DOI":"10.1038\/nature09135"},{"key":"2026041209582275000_2025.01.15.633135v2.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2010.12.003"},{"key":"2026041209582275000_2025.01.15.633135v2.7","doi-asserted-by":"crossref","unstructured":"Caiado, F. , E.M. Pietras , and M.G. Manz . 2021. Inflammation as a regulator of hematopoietic stem cell function in disease, aging, and clonal selection. Journal of Experimental Medicine 218:","DOI":"10.1084\/jem.20201541"},{"key":"2026041209582275000_2025.01.15.633135v2.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2007.10.003"},{"key":"2026041209582275000_2025.01.15.633135v2.9","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018016295"},{"key":"2026041209582275000_2025.01.15.633135v2.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.07.019"},{"key":"2026041209582275000_2025.01.15.633135v2.11","first-page":"D780","article-title":"Haemopedia RNA-seq: a database of gene expression during haematopoiesis in mice and humans","volume":"47","year":"2018","journal-title":"Nucleic Acids Research"},{"key":"2026041209582275000_2025.01.15.633135v2.12","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01643-14"},{"key":"2026041209582275000_2025.01.15.633135v2.13","doi-asserted-by":"crossref","unstructured":"Collins, A. , C.A. Mitchell , and E. Passegu\u00e9 . 2021. Inflammatory signaling regulates hematopoietic stem and progenitor cell development and homeostasis. Journal of Experimental Medicine 218:","DOI":"10.1084\/jem.20201545"},{"key":"2026041209582275000_2025.01.15.633135v2.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.02.002"},{"key":"2026041209582275000_2025.01.15.633135v2.15","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-019-0718-6"},{"key":"2026041209582275000_2025.01.15.633135v2.16","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1112169108"},{"key":"2026041209582275000_2025.01.15.633135v2.17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1703100114"},{"key":"2026041209582275000_2025.01.15.633135v2.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.05.019"},{"key":"2026041209582275000_2025.01.15.633135v2.19","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21908"},{"key":"2026041209582275000_2025.01.15.633135v2.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2007.10.007"},{"key":"2026041209582275000_2025.01.15.633135v2.21","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0904019"},{"key":"2026041209582275000_2025.01.15.633135v2.22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005507"},{"key":"2026041209582275000_2025.01.15.633135v2.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.01.067"},{"key":"2026041209582275000_2025.01.15.633135v2.24","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3960"},{"key":"2026041209582275000_2025.01.15.633135v2.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.06.014"},{"key":"2026041209582275000_2025.01.15.633135v2.26","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(03)00298-X"},{"key":"2026041209582275000_2025.01.15.633135v2.27","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019003910"},{"key":"2026041209582275000_2025.01.15.633135v2.28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3002517"},{"key":"2026041209582275000_2025.01.15.633135v2.29","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-8935-5_26"},{"key":"2026041209582275000_2025.01.15.633135v2.30","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-08-240903"},{"key":"2026041209582275000_2025.01.15.633135v2.31","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000505"},{"key":"2026041209582275000_2025.01.15.633135v2.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.12.031"},{"key":"2026041209582275000_2025.01.15.633135v2.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.09.062"},{"key":"2026041209582275000_2025.01.15.633135v2.34","doi-asserted-by":"publisher","DOI":"10.4049\/immunohorizons.1700054"},{"key":"2026041209582275000_2025.01.15.633135v2.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.02.011"},{"key":"2026041209582275000_2025.01.15.633135v2.36","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-01-328682"},{"key":"2026041209582275000_2025.01.15.633135v2.37","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01667-y"},{"key":"2026041209582275000_2025.01.15.633135v2.38","doi-asserted-by":"publisher","DOI":"10.1016\/S0037-1963(00)90086-6"},{"key":"2026041209582275000_2025.01.15.633135v2.39","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004110"},{"key":"2026041209582275000_2025.01.15.633135v2.40","doi-asserted-by":"crossref","unstructured":"Liu, G. , O. Abas , Y. Fu , Y. Chen , A.B. Strickland , D. Sun , and M. Shi . 2021. IL-27 Negatively Regulates Tip-DC Development during Infection. mBio 12:","DOI":"10.1128\/mBio.03385-20"},{"key":"2026041209582275000_2025.01.15.633135v2.41","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.585771"},{"key":"2026041209582275000_2025.01.15.633135v2.42","doi-asserted-by":"publisher","DOI":"10.1002\/stem.3169"},{"key":"2026041209582275000_2025.01.15.633135v2.43","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0028669"},{"key":"2026041209582275000_2025.01.15.633135v2.44","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001893"},{"key":"2026041209582275000_2025.01.15.633135v2.45","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-02-0456"},{"key":"2026041209582275000_2025.01.15.633135v2.46","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1799"},{"key":"2026041209582275000_2025.01.15.633135v2.47","doi-asserted-by":"publisher","DOI":"10.1002\/stem.2040"},{"key":"2026041209582275000_2025.01.15.633135v2.48","first-page":"1647","article-title":"Granulocyte colony-stimulating factor directly acts on mouse lymphoid-biased but not myeloid-biased hematopoietic stem cells","volume":"106","year":"2021","journal-title":"Haematologica"},{"key":"2026041209582275000_2025.01.15.633135v2.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2014.08.017"},{"key":"2026041209582275000_2025.01.15.633135v2.50","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.74561"},{"key":"2026041209582275000_2025.01.15.633135v2.51","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-022-00633-5"},{"key":"2026041209582275000_2025.01.15.633135v2.52","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1011820"},{"key":"2026041209582275000_2025.01.15.633135v2.53","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0701152104"},{"key":"2026041209582275000_2025.01.15.633135v2.54","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13017-4"},{"key":"2026041209582275000_2025.01.15.633135v2.55","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.4.2225"},{"key":"2026041209582275000_2025.01.15.633135v2.56","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(02)00324-2"},{"key":"2026041209582275000_2025.01.15.633135v2.57","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20131043"},{"key":"2026041209582275000_2025.01.15.633135v2.58","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12655"},{"key":"2026041209582275000_2025.01.15.633135v2.59","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2011.10.012"},{"key":"2026041209582275000_2025.01.15.633135v2.60","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07238-x"},{"key":"2026041209582275000_2025.01.15.633135v2.61","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3863"},{"key":"2026041209582275000_2025.01.15.633135v2.62","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.41258"},{"key":"2026041209582275000_2025.01.15.633135v2.63","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"2026041209582275000_2025.01.15.633135v2.64","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-06-093328"},{"key":"2026041209582275000_2025.01.15.633135v2.65","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01499"},{"key":"2026041209582275000_2025.01.15.633135v2.66","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1030640104"},{"key":"2026041209582275000_2025.01.15.633135v2.67","doi-asserted-by":"publisher","DOI":"10.1097\/MOH.0000000000000586"},{"key":"2026041209582275000_2025.01.15.633135v2.68","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2018.06.001"},{"key":"2026041209582275000_2025.01.15.633135v2.69","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.11.021"},{"key":"2026041209582275000_2025.01.15.633135v2.70","first-page":"123.128","article-title":"IL-27 limits neutrophil mediated pathology during pulmonary infection with Cryptococcus neoformans","volume":"198","year":"2017","journal-title":"The Journal of Immunology"},{"key":"2026041209582275000_2025.01.15.633135v2.71","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(03)00300-5"},{"key":"2026041209582275000_2025.01.15.633135v2.72","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81692-X"},{"key":"2026041209582275000_2025.01.15.633135v2.73","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20060471"},{"key":"2026041209582275000_2025.01.15.633135v2.74","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022017152"},{"key":"2026041209582275000_2025.01.15.633135v2.75","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2300176"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.01.15.633135","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:00:56Z","timestamp":1782277256000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.01.15.633135"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,19]]},"references-count":75,"URL":"https:\/\/doi.org\/10.1101\/2025.01.15.633135","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.7554\/eLife.105876","asserted-by":"subject"},{"id-type":"doi","id":"10.7554\/eLife.105876.3","asserted-by":"object"}],"has-version":[{"id-type":"doi","id":"10.7554\/eLife.105876.2","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.105876.1","asserted-by":"object"}]},"subject":[],"published":{"date-parts":[[2025,1,19]]},"subtype":"preprint"}}