{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:55:54Z","timestamp":1787313354056,"version":"build-2736575974"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2014\/00984-3, 2019\/18886-1, 2019\/09704-7, 2022\/06227-6"],"award-info":[{"award-number":["2014\/00984-3, 2019\/18886-1, 2019\/09704-7, 2022\/06227-6"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u03ccgico","doi-asserted-by":"publisher","award":["140594\/2019-1"],"award-info":[{"award-number":["140594\/2019-1"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Monocytes can interact with erythroid cells and contribute to macrophage pools under anemic stress, thereby supporting the erythropoietic niche. In sickle cell anemia (SCA), extensive hemolysis and ineffective erythropoiesis may expose circulating monocytes to abnormal red blood cells (RBCs), potentially altering their phenotype and function to accommodate the higher erythropoietic response and iron demand.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      We characterized circulating monocytes from SCA patients at steady state using flow cytometry and\n                      <jats:italic>in vitro<\/jats:italic>\n                      phagocytosis assays. Intracellular RBC material was detected in all circulating monocyte subsets from SCA patients, indicating active erythrophagocytosis. Mechanistically, SCA monocytes displayed upregulated VCAM-1 and reduced SIRP-\u03b1 expression, favoring RBC binding and internalization even when CD47 expression on RBCs was preserved. Following RBC engulfment, monocytes upregulated heme oxygenase-1 (HO-1) and ferroportin (FPN), consistent with enhanced heme degradation and iron export, and expressed higher levels of CD206, suggesting a regulatory phenotype.\n                      <jats:italic>In vitro<\/jats:italic>\n                      assays confirmed that both sickle RBCs and SCA monocytes synergistically promoted erythrophagocytosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Circulating monocytes from SCA patients undergo phenotypic and functional reprogramming upon interaction with sickled RBCs, acquiring features reminiscent of erythroblastic island macrophages. These findings highlight a previously underappreciated role for monocytes in RBC clearance, heme metabolism, and iron recycling in SCA, with potential implications for inflammation and disease progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1699306","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T05:13:20Z","timestamp":1764911600000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Monocyte\u2013red blood cell crosstalk supports clearance and heme metabolism in sickle cell anemia"],"prefix":"10.3389","volume":"16","author":[{"given":"Marina Dorigatti","family":"Borges","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matheus Ajeje","family":"de Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izabela Felice","family":"Paes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela Pinheiro","family":"Leonardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dulcin\u00e9ia Martins","family":"Albuquerque","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Lanaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara Teresinha Ollala","family":"Saad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Sesti-Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando Ferreira","family":"Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"key":"B1","first-page":"8","article-title":"Erythroblastic Island, functional unity of bone marrow","volume":"13","author":"Bessis","year":"1958","journal-title":"Rev Hematol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-03-077883","article-title":"Erythroblastic islands: Niches for erythropoiesis","volume":"112","author":"Chasis","year":"2008","journal-title":"Blood"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3057","article-title":"CD169 + macrophages provide a niche promoting erythropoiesis under homeostasis and stress","volume":"19","author":"Chow","year":"2013","journal-title":"Nat Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/nature03964","article-title":"Phosphatidylserine-dependent engulfment by macrophages of nuclei from erythroid precursor cells","volume":"437","author":"Yoshida","year":"2005","journal-title":"Nature"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.68.4.464","article-title":"Impaired splenic erythropoiesis in phlebotomized mice injected with CL2MDP-liposome: an experimental model for studying the role of stromal macrophages in erythropoiesis Abstract: Erythropoiesis occurs in the presence of erythropoietin ( EPO ) without m","volume":"68","author":"Sadahira","year":"2000","journal-title":"Jounal Leukocyte Biol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V84.10.3494.3494","article-title":"The association of erythroblasts with macrophages promotes erythroid proliferation and maturation: A 30-kD heparin-binding protein is involved in this contact","volume":"84","author":"Hanspal","year":"1994","journal-title":"Blood"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.99.1.141","article-title":"Expression of a divalent cation-dependent erythroblast adhesion receptor by stromal macrophages from murine bone marrow","volume":"99","author":"Morris","year":"1991","journal-title":"J Cell Sci"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1097\/MOH.0000000000000131","article-title":"Macrophages and regulation of erythropoiesis. 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