title: Mass Cytometry of the Human Mucosal Immune System Identifies Tissue- and Disease-Associated Immune Subsets.
abstract: Inflammatory intestinal diseases are characterized by abnormal immune responses and affect distinct locations of the gastrointestinal tract. Although the role of several immune subsets in driving intestinal pathology has been studied, a system-wide approach that simultaneously interrogates all major lineages on a single-cell basis is lacking. We used high-dimensional mass cytometry to generate a system-wide view of the human mucosal immune system in health and disease. We distinguished 142 immune subsets and through computational applications found distinct immune subsets in peripheral blood mononuclear cells and intestinal biopsies that distinguished patients from controls. In addition, mucosal lymphoid malignancies were readily detected as well as precursors from which these likely derived. These findings indicate that an integrated high-dimensional analysis of the entire immune system can identify immune subsets associated with the pathogenesis of complex intestinal disorders. This might have implications for diagnostic procedures, immune-monitoring, and treatment of intestinal diseases and mucosal malignancies.
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
authors.forename: Vincent
authors.initials: V
authors.lastname: van Unen
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
authors.forename: Ilse
authors.initials: I
authors.lastname: Molendijk
authors.affiliation: Department of Center for Proteomics, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
authors.forename: Mine
authors.initials: M
authors.lastname: Temurhan
authors.affiliation: Department of Pattern Recognition and Bioinformatics Group, Delft University of Technology, 2600 GA Delft, the Netherlands.
authors.forename: Thomas
authors.initials: T
authors.lastname: Höllt
authors.affiliation: Department of Gastroenterology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
authors.forename: Andrea E
authors.initials: AE
authors.lastname: van der Meulen-de Jong
authors.affiliation: Department of Gastroenterology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
authors.forename: Hein W
authors.initials: HW
authors.lastname: Verspaget
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Mearin
authors.affiliation: Department of Gastroenterology, VU Medical Center, 1081 HZ Amsterdam, the Netherlands.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Mulder
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: van Bergen
authors.affiliation: Department of LKEB Radiology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands; Department of Pattern Recognition and Bioinformatics Group, Delft University of Technology, 2600 GA Delft, the Netherlands.
authors.forename: Boudewijn P F
authors.initials: BP
authors.lastname: Lelieveldt
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands. Electronic address: f.koning@lumc.nl.
authors.forename: Frits
authors.initials: F
authors.lastname: Koning
mesh_terms: D000328:Adult; D000368:Aged; D002446:Celiac Disease / Q000175:diagnosis / Q000276:immunology*; D015331:Cohort Studies; D019295:Computational Biology; D003424:Crohn Disease / Q000175:diagnosis / Q000276:immunology*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D019044:Image Cytometry / Q000379:methods*; D007159:Immunologic Tests; D007413:Intestinal Mucosa / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology* / Q000502:physiology*; D016399:Lymphoma, T-Cell / Q000175:diagnosis / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015166:Monitoring, Immunologic; D009928:Organ Specificity; D059010:Single-Cell Analysis