2025
Humanization of CD47 enables development of functional human neutrophils via postirradiation remodeling of the bone marrow.
Sefik E, Philbrick W, Zhang F, Agrawal K, Van Lee B, Sam J, Karatepe K, Zheng Y, Liang K, Peng S, Mirza H, Rangavajhula A, Simon P, Arun N, Babu P, Eynon E, Chiorazzi M, Shan L, Halene S, Luo H, Rongvaux A, Kluger Y, Flavell R. Humanization of CD47 enables development of functional human neutrophils via postirradiation remodeling of the bone marrow. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2426546122. PMID: 40956886, PMCID: PMC12478129, DOI: 10.1073/pnas.2426546122.Peer-Reviewed Original ResearchConceptsBone marrowHuman CD47Human granulocyte-macrophage progenitorsHuman immune developmentMature human monocytesHuman neutrophilsHumanized mouse modelNeutrophil extracellular trap formationHuman hematopoietic stemGranulocyte-macrophage progenitorsHuman M-CSFHuman immune responseGenetically modified miceResponse to inflammationExtracellular trap formationHuman bone marrowCD47 promoterHuman immune systemPhysiological levelsNK cellsHumanized miceDendritic cellsHematopoietic stemMyeloid lineageHuman hematopoiesis
2024
The human CD47 checkpoint is targeted by an immunosuppressive Aedes aegypti salivary factor to enhance arboviral skin infectivity
Marin-Lopez A, Huck J, Esterly A, Azcutia V, Rosen C, Garcia-Milian R, Sefik E, Vidal-Pedrola G, Raduwan H, Chen T, Arora G, Halene S, Shaw A, Palm N, Flavell R, Parkos C, Thangamani S, Ring A, Fikrig E. The human CD47 checkpoint is targeted by an immunosuppressive Aedes aegypti salivary factor to enhance arboviral skin infectivity. Science Immunology 2024, 9: eadk9872-eadk9872. PMID: 39121194, PMCID: PMC11924945, DOI: 10.1126/sciimmunol.adk9872.Peer-Reviewed Original ResearchConceptsSuppress antiviral responsesArthropod proteinsPathogen replicationAntiviral responseProtein AVertebrate hostsMosquito salivary proteinsUp-regulatedBlood feedingHuman macrophagesPleomorphic effectsSkin infectionsZika virus disseminationInhibit proinflammatory responsesSalivary proteinsProteinNatural ligandWhite blood cellsHuman skin explantsProinflammatory responseMosquito salivaVirus disseminationHuman CD47Salivary factorsArbovirus infection
2021
Expression of human CD47 in pig glomeruli prevents proteinuria and prolongs graft survival following pig‐to‐baboon xenotransplantation
Takeuchi K, Ariyoshi Y, Shimizu A, Okumura Y, Cara‐Fuentes G, Garcia G, Pomposelli T, Watanabe H, Boyd L, Ekanayake‐Alper D, Amarnath D, Sykes M, Sachs D, Johnson R, Yamada K. Expression of human CD47 in pig glomeruli prevents proteinuria and prolongs graft survival following pig‐to‐baboon xenotransplantation. Xenotransplantation 2021, 28: e12708. PMID: 34418164, PMCID: PMC8957703, DOI: 10.1111/xen.12708.Peer-Reviewed Original ResearchConceptsDevelopment of proteinuriaKidney graftsRenal tubular cellsGlomerular cellsTubular cellsNephrotic syndromeHuman CD47Transgene expressionPig-to-baboon xenotransplantationBone marrow transplantationDestructive inflammatory responseUpregulation of CD80Pig-to-baboonSMPDL-3bPigsMarrow transplantationGalT-KOGraft survivalProlonged survivalAntibody administrationThymic graftsHCD47Kidney xenotransplantationVascularized thymic graftsGroup B
2019
Intra‐bone bone marrow transplantation from hCD47 transgenic pigs to baboons prolongs chimerism to >60 days and promotes increased porcine lung transplant survival
Watanabe H, Ariyoshi Y, Pomposelli T, Takeuchi K, Ekanayake‐Alper D, Boyd L, Arn S, Sahara H, Shimizu A, Ayares D, Lorber M, Sykes M, Sachs D, Yamada K. Intra‐bone bone marrow transplantation from hCD47 transgenic pigs to baboons prolongs chimerism to >60 days and promotes increased porcine lung transplant survival. Xenotransplantation 2019, 27: e12552. PMID: 31544995, PMCID: PMC7007336, DOI: 10.1111/xen.12552.Peer-Reviewed Original ResearchConceptsLung xenograft survivalAnti-pig antibody levelsPig-to-baboonBone marrow transplantationNegative pigsLung xenograftsMarrow transplantationXenograft survivalPigsPig-to-baboon modelHCD47B cell toleranceLung transplant survivalCellular unresponsivenessAntibody responseLungs 1Antibody levelsGraft survivalProlonged survivalAnimalsT cellsHuman CD47MacrochimerismExtended survivalDays
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