1. Mass Cytometry of the Human Mucosal Immune System Identifies Tissue- and Disease-Associated Immune Subsets
- Author
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Thomas Höllt, Chris J. J. Mulder, Ilse Molendijk, Jeroen van Bergen, Hein W. Verspaget, Mine Temurhan, Andrea E. van der Meulen-de Jong, Boudewijn P. F. Lelieveldt, Vincent van Unen, Na Li, M. Luisa Mearin, Frits Koning, Gastroenterology and hepatology, and AGEM - Digestive immunity
- Subjects
Adult ,Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,animal diseases ,Immunology ,chemical and pharmacologic phenomena ,Disease ,Immunologic Tests ,Biology ,Lymphoma, T-Cell ,Peripheral blood mononuclear cell ,Cohort Studies ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Crohn Disease ,Intestinal mucosa ,Monitoring, Immunologic ,medicine ,Humans ,Immunology and Allergy ,Mass cytometry ,Lymphocytes ,Intestinal Mucosa ,Aged ,Image Cytometry ,Gastrointestinal tract ,Computational Biology ,Middle Aged ,biochemical phenomena, metabolism, and nutrition ,Lymphocyte Subsets ,3. Good health ,Celiac Disease ,HEK293 Cells ,030104 developmental biology ,Infectious Diseases ,Organ Specificity ,030220 oncology & carcinogenesis ,bacteria ,Female ,Single-Cell Analysis ,Intestinal Disorder - 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.
- Published
- 2016
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