title: Specific phenotype and function of CD56-expressing innate immune cell subsets in human thymus.
abstract: Whereas innate immune cells, such as NK and innate lymphoid cells (ILCs), have been characterized in different human tissues, knowledge on the thymic CD56-expressing cell subsets is limited. In this study, the rare subpopulations of thymic CD56+CD3-cells from samples of >100 patients have been successfully analyzed. The results revealed fundamental differences between thymic and peripheral blood (PB) CD56+CD3-cells. Thymic tissues lacked immunoregulatory CD56highCD16dimNK cells but showed two Eomes+CD56dimsubsets on which common NK cell markers were significantly altered. CD56dimCD16highcells expressed high amounts of NKG2A, NKG2D, and CD27 with low CD57. Conversely, CD56dimCD16dimcells displayed high CD127 but low expression of KIR, NKG2D, and natural cytotoxicity receptors (NCRs). Thymic CD56+CD3-cells were able to gain cytotoxicity but were especially immunoregulatory cells, producing a broad range of cytokines. Finally, one population of thymic CD56+cells resembled conventional NK cells, whereas the other represented a novel, noncanonical NK subset.
authors.affiliation: Department of Internal Medicine 5, Hematology and Oncology, Friedrich-Alexander Universität Erlangen-Nürnberg, University Hospital Erlangen, Erlangen, Germany.|Division of Stem Cell Transplantation and Immunology, Department for Children and Adolescents Medicine, University Hospital Frankfurt, Goethe University, Frankfurt, Germany.|Laboratory for Cellular Immunology, LOEWE Center for Cell and Gene Therapy, Goethe University, Frankfurt, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Gerstner
authors.affiliation: Department of Internal Medicine 5, Hematology and Oncology, Friedrich-Alexander Universität Erlangen-Nürnberg, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Köhler
authors.affiliation: Laboratory of Dendritic Cell Biology, Department of Dermatology, Friedrich-Alexander Universität Erlangen-Nürnberg, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Gordon
authors.initials: G
authors.lastname: Heidkamp
authors.affiliation: Department of Pediatric Heart Surgery, Friedrich-Alexander Universität Erlangen-Nürnberg, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Ariawan
authors.initials: A
authors.lastname: Purbojo
authors.affiliation: Laboratory for Cellular Immunology, LOEWE Center for Cell and Gene Therapy, Goethe University, Frankfurt, Germany.|Institute of Cardiovascular Regeneration, Centre for Molecular Medicine, Goethe University, Frankfurt, Germany.
authors.forename: Shizuka
authors.initials: S
authors.lastname: Uchida
authors.affiliation: Institute of Human Genetics, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Arif B
authors.initials: AB
authors.lastname: Ekici
authors.affiliation: Laboratory of Dendritic Cell Biology, Department of Dermatology, Friedrich-Alexander Universität Erlangen-Nürnberg, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Heger
authors.affiliation: Innate Immunity, Deutsches Rheuma-Forschungszentrum-Leibniz-Gemeinschaft, Berlin, Germany.
authors.forename: Merlin
authors.initials: M
authors.lastname: Luetke-Eversloh
authors.affiliation: University Hospital Frankfurt/Main, Department for Children and Adolescents Medicine, Pulmonology, Allergy and Cystic Fibrosis, Goethe University, Frankfurt, Germany; and.
authors.forename: Ralf
authors.initials: R
authors.lastname: Schubert
authors.affiliation: Division of Stem Cell Transplantation and Immunology, Department for Children and Adolescents Medicine, University Hospital Frankfurt, Goethe University, Frankfurt, Germany.|Laboratory for Cellular Immunology, LOEWE Center for Cell and Gene Therapy, Goethe University, Frankfurt, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bader
authors.affiliation: Division of Stem Cell Transplantation and Immunology, Department for Children and Adolescents Medicine, University Hospital Frankfurt, Goethe University, Frankfurt, Germany.|Laboratory for Cellular Immunology, LOEWE Center for Cell and Gene Therapy, Goethe University, Frankfurt, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Klingebiel
authors.affiliation: Institute of Cellular Therapeutics, Integrated Research and Treatment Center Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Koehl
authors.affiliation: Department of Internal Medicine 5, Hematology and Oncology, Friedrich-Alexander Universität Erlangen-Nürnberg, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Mackensen
authors.affiliation: Innate Immunity, Deutsches Rheuma-Forschungszentrum-Leibniz-Gemeinschaft, Berlin, Germany.
authors.forename: Chiara
authors.initials: C
authors.lastname: Romagnani
authors.affiliation: Department of Pediatric Heart Surgery, Friedrich-Alexander Universität Erlangen-Nürnberg, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Cesnjevar
authors.affiliation: Laboratory of Dendritic Cell Biology, Department of Dermatology, Friedrich-Alexander Universität Erlangen-Nürnberg, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Dudziak
authors.affiliation: Department of Internal Medicine 5, Hematology and Oncology, Friedrich-Alexander Universität Erlangen-Nürnberg, University Hospital Erlangen, Erlangen, Germany; evelyn.ullrich@kgu.de.|Division of Stem Cell Transplantation and Immunology, Department for Children and Adolescents Medicine, University Hospital Frankfurt, Goethe University, Frankfurt, Germany.|Laboratory for Cellular Immunology, LOEWE Center for Cell and Gene Therapy, Goethe University, Frankfurt, Germany.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Ullrich
mesh_terms: D000328:Adult; D000375:Aging / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis; D019002:CD56 Antigen / Q000032:analysis*; D015550:Cell Degranulation; D002469:Cell Separation; D002648:Child; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D007694:Killer Cells, Natural / Q000145:classification / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D055607:Receptors, Natural Killer Cell / Q000032:analysis; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D019002:CD56 Antigen; D016207:Cytokines; C522918:NCAM1 protein, human; D055607:Receptors, Natural Killer Cell
keywords: Eomes; ILC; NK cell; NKp46