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      Single-cell mass cytometry on peripheral blood identifies immune cell subsets associated with primary biliary cholangitis

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          Abstract

          The relationship between primary biliary cholangitis (PBC), a chronic cholestatic autoimmune liver disease, and the peripheral immune system remains to be fully understood. Herein, we performed the first mass cytometry (CyTOF)-based, immunophenotyping analysis of the peripheral immune system in PBC at single-cell resolution. CyTOF was performed on peripheral blood mononuclear cells (PBMCs) from PBC patients (n = 33) and age-/sex-matched healthy controls (n = 33) to obtain immune cell abundance and marker expression profiles. Hierarchical clustering methods were applied to identify immune cell types and subsets significantly associated with PBC. Subsets of gamma-delta T cells (CD3 +TCRgd +), CD8 + T cells (CD3 +CD8 +CD161 +PD1 +), and memory B cells (CD3 CD19 +CD20 +CD24 +CD27 +) were found to have lower abundance in PBC than in control. In contrast, higher abundance of subsets of monocytes and naïve B cells were observed in PBC compared to control. Furthermore, several naïve B cell (CD3 CD19 +CD20 +CD24 CD27 ) subsets were significantly higher in PBC patients with cirrhosis (indicative of late-stage disease) than in those without cirrhosis. Alternatively, subsets of memory B cells were lower in abundance in cirrhotic relative to non-cirrhotic PBC patients. Future immunophenotyping investigations could lead to better understanding of PBC pathogenesis and progression, and also to the discovery of novel biomarkers and treatment strategies.

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          Most cited references31

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          Primary Biliary Cholangitis: 2018 Practice Guidance from the American Association for the Study of Liver Diseases

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            Human regulatory B cells in health and disease: therapeutic potential

            Regulatory B cells (Bregs) modulate immune responses predominantly, although not exclusively, via the release of IL-10. The importance of human Bregs in the maintenance of immune homeostasis comes from a variety of immune-related pathologies, such as autoimmune diseases, cancers, and chronic infections that are often associated with abnormalities in Breg numbers or function. A continuous effort toward understanding Breg biology in healthy individuals will provide new opportunities to develop Breg immunotherapy that could prove beneficial in treating various immune-mediated pathologies. In this Review, we discuss findings regarding human Bregs, including their mechanisms of suppression and role in different disease settings. We also propose several therapeutic strategies targeting Bregs for better management of immune disorders.
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              Nonclassical Monocytes in Health and Disease

              Monocytes are innate blood cells that maintain vascular homeostasis and are early responders to pathogens in acute infections. There are three well-characterized classes of monocytes: classical (CD14 + CD16 − in humans and Ly6C hi in mice), intermediate (CD14 + CD16 + in humans and Ly6C + Treml4 + in mice), and nonclassical (CD14 − CD16 + in humans and Ly6C lo in mice). Classical monocytes are critical for the initial inflammatory response. Classical monocytes can differentiate into macrophages in tissue and can contribute to chronic disease. Nonclassical monocytes have been widely viewed as anti-inflammatory, as they maintain vascular homeostasis. They are a first line of defense in recognition and clearance of pathogens. However, their roles in chronic disease are less clear. They have been shown to be protective as well as positively associated with disease burden. This review focuses on the state of the monocyte biology field and the functions of monocytes, particularly nonclassical monocytes, in health and disease.
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                Author and article information

                Contributors
                Sung.Jaeyun@mayo.edu
                Lazaridis.Konstantinos@mayo.edu
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                28 July 2020
                28 July 2020
                2020
                : 10
                : 12584
                Affiliations
                [1 ]ISNI 0000 0004 0459 167X, GRID grid.66875.3a, Medical Genome Facility, Center for Individualized Medicine, , Mayo Clinic, ; Rochester, MN USA
                [2 ]ISNI 0000 0004 0459 167X, GRID grid.66875.3a, Department of Laboratory Medicine and Pathology, , Mayo Clinic, ; Rochester, MN USA
                [3 ]ISNI 0000 0004 0459 167X, GRID grid.66875.3a, Division of Gastroenterology and Hepatology, Department of Internal Medicine, , Mayo Clinic, ; 200 First Street SW, Rochester, MN 55905 USA
                [4 ]ISNI 0000 0004 0459 167X, GRID grid.66875.3a, Graduate Research Education Program (GREP), , Mayo Clinic, ; Rochester, MN USA
                [5 ]ISNI 0000000419368657, GRID grid.17635.36, Department of Computer Science and Engineering, , University of Minnesota Twin-Cities, ; Minneapolis, MN USA
                [6 ]ISNI 0000 0004 0459 167X, GRID grid.66875.3a, Microbiome Program, Center for Individualized Medicine, , Mayo Clinic, ; Rochester, MN USA
                [7 ]ISNI 0000 0004 0459 167X, GRID grid.66875.3a, Division of Surgical Research, Department of Surgery, , Mayo Clinic, ; 200 First Street SW, Rochester, MN 55905 USA
                [8 ]ISNI 0000 0004 0459 167X, GRID grid.66875.3a, Division of Pulmonary and Critical Care Medicine, Department of Medicine, , Mayo Clinic, ; Rochester, MN USA
                [9 ]ISNI 0000 0004 0459 167X, GRID grid.66875.3a, Department of Immunology, , Mayo Clinic, ; Rochester, MN USA
                [10 ]ISNI 0000 0001 2152 9905, GRID grid.50956.3f, Division of Digestive and Liver Diseases, Department of Medicine, , Cedars Sinai Medical Center, ; Los Angeles, CA USA
                [11 ]ISNI 0000 0004 0459 167X, GRID grid.66875.3a, Department of Obstetrics and Gynecology, , Mayo Clinic, ; Rochester, MN USA
                [12 ]ISNI 0000 0004 0459 167X, GRID grid.66875.3a, Division of Rheumatology, Department of Medicine, , Mayo Clinic, ; Rochester, MN USA
                Article
                69358
                10.1038/s41598-020-69358-4
                7387528
                c056907f-d16f-4f83-afe5-4144b80f3dec
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 3 February 2020
                : 7 July 2020
                Funding
                Funded by: Mayo Clinic Center for Individualized Medicine
                Funded by: National Institutes of Health
                Award ID: K12 HD065987
                Award Recipient :
                Funded by: Mark E. and Mary A.Davis to Mayo Clinic Center for Individualized Medicine
                Funded by: Everett J. and Jane M. Hauck Associate Director endowment for the Center for Individualized Medicine, Mayo Clinic
                Funded by: William O. Lund, Jr. and Natalie C. Lund Charitable Foundation endowment for the Center for Individualized Medicine, Mayo Clinic
                Categories
                Article
                Custom metadata
                © The Author(s) 2020

                Uncategorized
                computational biology and bioinformatics,gastroenterology
                Uncategorized
                computational biology and bioinformatics, gastroenterology

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