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A biliary immune landscape map of primary sclerosing cholangitis reveals a dominant network of neutrophils and tissue-resident T cells

Zimmer, Christine L. (author)
Karolinska Univ Hosp, Sweden,Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
von Seth, Erik (author)
Karolinska Institutet,Karolinska Univ Hosp, Sweden; Karolinska Univ Hosp, Sweden
Buggert, Marcus (author)
Karolinska Institutet,Karolinska Univ Hosp, Sweden
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Strauss, Otto (author)
Karolinska Univ Hosp, Sweden,Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
Hertwig, Laura (author)
Karolinska Univ Hosp, Sweden,Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
Nguyen, Son (author)
Univ Penn, PA 19104 USA; Univ Penn, PA 19104 USA,Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, PA 19104-6076, Philadelphia, United States; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
Wong, Alicia Y. W. (author)
Karolinska Inst, Sweden,Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
Zotter, Chiara (author)
Karolinska Univ Hosp, Sweden,Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
Berglin, Lena (author)
Karolinska Univ Hosp, Sweden,Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
Michaelsson, Jakob (author)
Karolinska Institutet,Karolinska Univ Hosp, Sweden
Hansson, Marcus Reuterwall (author)
Karolinska Institutet,Karolinska Inst, Sweden
Arnelo, Urban (author)
Karolinska Institutet,Umeå universitet,Kirurgi,Division of Surgery, Department of Clinical Science, Technology, Karolinska Institutet, Stockholm, Sweden,Karolinska Inst, Sweden; Umea Univ, Sweden
Sparrelid, Ernesto (author)
Karolinska Institutet,Karolinska Inst, Sweden
Ellis, Ewa C. S. (author)
Karolinska Inst, Sweden,Division of Transplantation Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
Söderholm, Johan D (author)
Linköpings universitet,Avdelningen för kirurgi, ortopedi och onkologi,Medicinska fakulteten,Region Östergötland, Kirurgiska kliniken US,Department of Biomedical and Clinical Sciences, Linköping University, 58183 Linköping, Sweden; Department of Surgery, Linköping University Hospital, 58185 Linköping, Sweden
Keita, Åsa (author)
Linköpings universitet,Avdelningen för kirurgi, ortopedi och onkologi,Medicinska fakulteten,Department of Biomedical and Clinical Sciences, Linköping University, 58183 Linköping, Sweden
Holm, Kristian (author)
Univ Oslo, Norway; Oslo Univ Hosp, Norway,Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Norwegian PSC Research Center, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
Ozenci, Volkan (author)
Karolinska Institutet,Karolinska Inst, Sweden
Hov, Johannes R. (author)
Univ Oslo, Norway; Oslo Univ Hosp, Norway; Oslo Univ Hosp, Norway; Oslo Univ Hosp, Norway,Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Norwegian PSC Research Center, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway; Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway
Mold, Jeff E. (author)
Karolinska Institutet,Karolinska Inst, Sweden
Cornillet, Martin (author)
Karolinska Univ Hosp, Sweden,Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
Ponzetta, Andrea (author)
Karolinska Univ Hosp, Sweden,Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
Bergquist, Annika (author)
Karolinska Institutet,Karolinska Univ Hosp, Sweden; Karolinska Univ Hosp, Sweden
Bjorkstrom, Niklas K. (author)
Karolinska Institutet,Karolinska Univ Hosp, Sweden
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 (creator_code:org_t)
AMER ASSOC ADVANCEMENT SCIENCE, 2021
2021
English.
In: Science Translational Medicine. - : AMER ASSOC ADVANCEMENT SCIENCE. - 1946-6234 .- 1946-6242. ; 13:599
Related links:
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • The human biliary system, a mucosal barrier tissue connecting the liver and intestine, is an organ often affected by serious inflammatory and malignant diseases. Although these diseases are linked to immunological processes, the biliary system represents an unexplored immunological niche. By combining endoscopy-guided sampling of the biliary tree with a high-dimensional analysis approach, comprehensive mapping of the human biliary immunological landscape in patients with primary sclerosing cholangitis (PSC), a severe biliary inflammatory disease, was conducted. Major differences in immune cell composition in bile ducts compared to blood were revealed. Furthermore, biliary inflammation in patients with PSC was characterized by high presence of neutrophils and T cells as compared to control individuals without PSC. The biliary T cells displayed a CD103(+)CD69(+) effector memory phenotype, a combined gut and liver homing profile, and produced interleukin-17 (IL-17) and IL-22. Biliary neutrophil infiltration in PSC associated with CXCL8, possibly produced by resident T cells, and CXCL16 was linked to the enrichment of T cells. This study uncovers the immunological niche of human bile ducts, defines a local immune network between neutrophils and biliary-resident T cells in PSC, and provides a resource for future studies of the immune responses in biliary disorders.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Gastroenterologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)

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