{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T21:32:47Z","timestamp":1791581567960,"version":"4.3.4"},"reference-count":34,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["21-15-00087"],"award-info":[{"award-number":["21-15-00087"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Erythroid cells are emerging players in immunological regulation that have recently been shown to play a crucial role in fetomaternal tolerance in mice. In this work, we set ourselves the goal of discovering additional information about the molecular mechanisms of this process. We used flow cytometry to study placental erythroid cells\u2019 composition and BioPlex for the secretome profiling of 23 cytokines at E12.5 and E19.5 in both allogeneic and syngeneic pregnancies. We found that (1) placental erythroid cells are mainly represented by CD45+ erythroid cells; (2) the secretomes of CD71+ placental erythroid cells differ from the ones in syngeneic pregnancy; (3) CCL2, CCL3, CCL4 and CXCL1 chemokines were secreted on each day of embryonic development and in both types of pregnancy studied. We believe that these chemokines lure placental immune cells towards erythroid cells so that erythroid cells can induce anergy in those immune cells via cell-bound ligands such as PD-L1, enzymes such as ARG1, and secreted factors such as TGF\u03b2-1.<\/jats:p>","DOI":"10.3390\/ijms24098130","type":"journal-article","created":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T13:54:46Z","timestamp":1682949286000},"page":"8130","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Murine Placental Erythroid Cells Are Mainly Represented by CD45+ Immunosuppressive Erythroid Cells and Secrete CXCL1, CCL2, CCL3 and CCL4 Chemokines"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7175-4051","authenticated-orcid":false,"given":"Kirill","family":"Nazarov","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Immunology, Federal State Budgetary Scientific Institution, Research Institute of Fundamental and Clinical Immunology, Novosibirsk 630099, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5055-4859","authenticated-orcid":false,"given":"Roman","family":"Perik-Zavodskii","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, Federal State Budgetary Scientific Institution, Research Institute of Fundamental and Clinical Immunology, Novosibirsk 630099, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4911-1994","authenticated-orcid":false,"given":"Olga","family":"Perik-Zavodskaia","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, Federal State Budgetary Scientific Institution, Research Institute of Fundamental and Clinical Immunology, Novosibirsk 630099, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0788-5385","authenticated-orcid":false,"given":"Saleh","family":"Alrhmoun","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, Federal State Budgetary Scientific Institution, Research Institute of Fundamental and Clinical Immunology, Novosibirsk 630099, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1683-8951","authenticated-orcid":false,"given":"Marina","family":"Volynets","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, Federal State Budgetary Scientific Institution, Research Institute of Fundamental and Clinical Immunology, Novosibirsk 630099, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Shevchenko","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, Federal State Budgetary Scientific Institution, Research Institute of Fundamental and Clinical Immunology, Novosibirsk 630099, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7366-7768","authenticated-orcid":false,"given":"Sergey","family":"Sennikov","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, Federal State Budgetary Scientific Institution, Research Institute of Fundamental and Clinical Immunology, Novosibirsk 630099, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"20140066","DOI":"10.1098\/rstb.2014.0066","article-title":"The placenta: A multifaceted, transient organ","volume":"370","author":"Burton","year":"2015","journal-title":"Philos. Trans. R. Soc. B Biol. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.4049\/jimmunol.119.5.1659","article-title":"Allogeneic pregnancy as immunoabsorbent","volume":"119","author":"Wegmann","year":"1977","journal-title":"J. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.3389\/fimmu.2018.02087","article-title":"Decidual-placental immune landscape during syngeneic murine pregnancy","volume":"9","author":"Li","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"42941","DOI":"10.1038\/srep42941","article-title":"Cytotrophoblast, not syncytiotrophoblast, dominates glycolysis and oxidative phosphorylation in human term placenta","volume":"7","author":"Kolahi","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_5","first-page":"3321","article-title":"The first trimester human placenta is a site for terminal maturation of primitive erythroid cells","volume":"116","author":"Prashad","year":"2010","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.devcel.2011.12.022","article-title":"Trophoblasts regulate the placental hematopoietic niche through PDGF-B signaling","volume":"22","author":"Chhabra","year":"2012","journal-title":"Dev. Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1046\/j.1365-2141.2000.02037.x","article-title":"The monoclonal antibody TER-119 recognizes a molecule associated with glycophorin A and specifically marks the late stages of murine erythroid lineage","volume":"109","author":"Kina","year":"2000","journal-title":"Br. J. Hematol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4044","DOI":"10.4049\/jimmunol.1800113","article-title":"CD71+ Erythroid suppressor cells promote fetomaternal tolerance through arginase-2 and PDL-1","volume":"200","author":"Delyea","year":"2018","journal-title":"J. Immunol."},{"key":"ref_9","first-page":"771","article-title":"Cytokine gene expression in erythroid cells","volume":"7","author":"Sennikov","year":"1996","journal-title":"Eur. Cytokine Netw."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2121-5-39","article-title":"Production of hemo-and immunoregulatory cytokines by erythroblast antigen+ and glycophorin A+ cells from human bone marrow","volume":"5","author":"Sennikov","year":"2004","journal-title":"BMC Cell Biol."},{"key":"ref_11","first-page":"274","article-title":"Production of cytokines by immature erythroid cells derived from human embryonic liver","volume":"12","author":"Sennikov","year":"2001","journal-title":"Eur. Cytokine Netw."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1111\/aji.12562","article-title":"In vivo T-cell activation by a monoclonal \u03b1CD3\u03b5 antibody induces preterm labor and birth","volume":"76","author":"Romero","year":"2016","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1093\/ecco-jcc\/jjy147","article-title":"Lower abundance and impaired function of CD71+ erythroid cells in inflammatory bowel disease patients during pregnancy","volume":"13","author":"Dunsmore","year":"2019","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1002\/JLB.5A0717-291RRR","article-title":"CD71+ erythroid cells from neonates born to women with preterm labor regulate cytokine and cellular responses","volume":"103","author":"Miller","year":"2018","journal-title":"J. Leukoc. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1007\/s10544-015-0021-3","article-title":"Isolation of nucleated red blood cells in maternal blood for Non-invasive prenatal diagnosis","volume":"17","author":"Byeon","year":"2015","journal-title":"Biomed. Microdevices"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/S0171-2985(98)80045-4","article-title":"Characterization of erythroid cell-derived natural suppressor activity","volume":"198","author":"Seledtsov","year":"1998","journal-title":"Immunobiology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1016\/j.imbio.2016.04.004","article-title":"Immunoregulatory function of neonatal nucleated red blood cells in humans","volume":"221","author":"Cui","year":"2016","journal-title":"Immunobiology"},{"key":"ref_18","first-page":"421","article-title":"Nucleated red blood cells are a direct response to mediators of inflammation in newborn","volume":"198","author":"Dulay","year":"2008","journal-title":"Gynecology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1095\/biolreprod.109.076976","article-title":"Pregnancy alters the proliferation and apoptosis of mouse splenic erythroid lineage cells and leukocytes","volume":"81","author":"Norton","year":"2009","journal-title":"Biol. Reprod."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3392","DOI":"10.1172\/JCI94027","article-title":"27-Hydroxycholesterol induces hematopoietic stem cell mobilization and extramedullary hematopoiesis during pregnancy","volume":"127","author":"Oguro","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"573","DOI":"10.3389\/fimmu.2019.00573","article-title":"New paradigm in the role of regulatory T cells during pregnancy","volume":"10","author":"Tsuda","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.3389\/fimmu.2020.01182","article-title":"Regulatory T cells in pregnancy: It is not all about FoxP3","volume":"11","author":"Krop","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3021","DOI":"10.1002\/eji.200737810","article-title":"IL-35 is a novel cytokine with therapeutic effects against collagen-induced arthritis through the expansion of regulatory T cells and suppression of Th17 cells","volume":"37","author":"Niedbala","year":"2007","journal-title":"Eur. J. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.canlet.2020.12.003","article-title":"Intratumoral CD45+CD71+ erythroid cells induce immune tolerance and predict tumor recurrence in hepatocellular carcinoma","volume":"499","author":"Chen","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1093\/humrep\/det060","article-title":"Control of extravillous trophoblast function by the eotaxins CCL11, CCL24 and CCL26","volume":"28","author":"Chau","year":"2013","journal-title":"Hum. Reprod."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4950","DOI":"10.4049\/jimmunol.154.10.4950","article-title":"IL-12 directly enhances in vitro murine erythropoiesis in combination with IL-4 and stem cell factor","volume":"154","author":"Dybedal","year":"1995","journal-title":"J. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1111\/j.1365-2141.1990.tb02578.x","article-title":"Interleukin-4 suppresses the interleukin-3 dependent erythroid colony formation from normal human bone marrow cells","volume":"74","author":"Beentjes","year":"1990","journal-title":"Br. J. Haematol."},{"key":"ref_28","first-page":"781","article-title":"Actions of human interleukin-4\/B-cell stimulatory factor-1 on proliferation and differentiation of enriched hematopoietic progenitor cells in culture","volume":"96","author":"Sonoda","year":"1997","journal-title":"Blood"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1038\/leu.2016.81","article-title":"Leukemia cell infiltration causes defective erythropoiesis partially through MIP-1\u03b1\/CCL3","volume":"30","author":"Wang","year":"2016","journal-title":"Leukemia"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1111\/j.1582-4934.2012.01650.x","article-title":"Myometrial immune cells contribute to term parturition, preterm labour and post-partum involution in mice","volume":"17","author":"Shynlova","year":"2013","journal-title":"J. Cell. Mol. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"864","DOI":"10.4049\/jimmunol.1901530","article-title":"A comprehensive workflow for applying single-cell clustering and pseudotime analysis to flow cytometry data","volume":"205","author":"Melsen","year":"2020","journal-title":"J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1111\/cgf.12893","article-title":"Cytosplore: Interactive immune cell phenotyping for large single-cell datasets","volume":"35","author":"Pezzotti","year":"2016","journal-title":"Comput. Graph. Forum"},{"key":"ref_33","unstructured":"Bedre, R. (2022). Bioinformatics data analysis and visualization toolkit (2.0.9). Zenodo."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"btac757","DOI":"10.1093\/bioinformatics\/btac757","article-title":"GSEApy: A comprehensive package for performing gene set enrichment analysis in Python","volume":"39","author":"Fang","year":"2023","journal-title":"Bioinformatics"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/9\/8130\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:27:51Z","timestamp":1760124471000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/9\/8130"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,1]]},"references-count":34,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["ijms24098130"],"URL":"https:\/\/doi.org\/10.3390\/ijms24098130","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,1]]}}}