title: Induced Human Decidual NK-Like Cells Improve Utero-Placental Perfusion in Mice.
abstract: Decidual NK (dNK) cells, a distinct type of NK cell, are thought to regulate uterine spiral artery remodeling, a process that allows for increased blood delivery to the fetal-placental unit. Impairment of uterine spiral artery remodeling is associated with decreased placental perfusion, increased uterine artery resistance, and obstetric complications such as preeclampsia and intrauterine growth restriction. Ex vivo manipulation of human peripheral blood NK (pNK) cells by a combination of hypoxia, TGFß-1 and 5-aza-2'-deoxycytidine yields cells with phenotypic and in vitro functional similarities to dNK cells, called idNK cells. Here, gene expression profiling shows that CD56Bright idNK cells derived ex vivo from human pNK cells, and to a lesser extent CD56Dim idNK cells, are enriched in the gene expression signature that distinguishes dNK cells from pNK cells. When injected into immunocompromised pregnant mice with elevated uterine artery resistance, idNK cells homed to the uterus and reduced the uterine artery resistance index, suggesting improved placental perfusion.
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States of America.
authors.forename: Ricardo C
authors.initials: RC
authors.lastname: Cavalli
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States of America.|Gulbenkian Programme for Advanced Medical Education, Lisbon, Portugal.
authors.forename: Ana Sofia
authors.initials: AS
authors.lastname: Cerdeira
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States of America.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Pernicone
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States of America.
authors.forename: Henri A
authors.initials: HA
authors.lastname: Korkes
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States of America.|Howard Hughes Medical Institute, Chevy Chase, MD, United States of America.
authors.forename: Suzanne D
authors.initials: SD
authors.lastname: Burke
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States of America.|Howard Hughes Medical Institute, Chevy Chase, MD, United States of America.
authors.forename: Augustine
authors.initials: A
authors.lastname: Rajakumar
authors.affiliation: Division of Nephrology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America.
authors.forename: Ravi I
authors.initials: RI
authors.lastname: Thadhani
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America.
authors.forename: Drucilla J
authors.initials: DJ
authors.lastname: Roberts
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States of America.
authors.forename: Manoj
authors.initials: M
authors.lastname: Bhasin
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States of America.|Howard Hughes Medical Institute, Chevy Chase, MD, United States of America.
authors.forename: S Ananth
authors.initials: SA
authors.lastname: Karumanchi
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States of America.
authors.forename: Hernan D
authors.identifier: http://orcid.org/0000-0003-0060-8801
authors.initials: HD
authors.lastname: Kopcow
mesh_terms: D000818:Animals; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019002:CD56 Antigen / Q000235:genetics*; D015687:Cell Hypoxia; D003656:Decidua / Q000098:blood supply / Q000276:immunology*; D000077209:Decitabine; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D006801:Humans; D016867:Immunocompromised Host; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000637:transplantation*; D051379:Mice; D010920:Placenta / Q000098:blood supply* / Q000276:immunology; D011247:Pregnancy; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D019002:CD56 Antigen; C522918:NCAM1 protein, human; D016212:Transforming Growth Factor beta; D000077209:Decitabine; D001374:Azacitidine