Journal Article Ahead of print 4 citations
PubMed: 42447860 DOI: 10.1016/j.immuni.2026.06.013
Antigen-restricted Candida albicans Th17 cells link oral-gut immunity and adopt pathogenic features during intestinal inflammation.
Immunity
Authors: Gabriela Rios Martini, Philipp Hofmann, Ann-Kristin Kamps, Amos Weichberger, Ekaterina Tikhonova, Aidan Conroy, Xiangyu Pan, Diana Milagros Namuch, Laura Rathjens, Arne Bergfeld, Susanna Nikolaus, Jeanette Riffert, Florian Tran, Konrad Aden, Maria Witte, Clemens Schafmayer, Dora Stölzl, Stephan Weidinger, Markus M Heimesaat, Miriam Cyris, Ann-Kristin Härdter, Christof Dörfer, Robert Zarnowski, David Andes, Sascha Brunke, Bernhard Hube, Alexander Scheffold, Iliyan D Iliev, Stefan Schreiber, Petra Bacher
Affiliations
- Institute of Medical Immunology, Christian-Albrecht-University of Kiel, Kiel, Germany; Institute of Clinical Molecular Biology, Christian-Albrecht-University of Kiel, Kiel, Germany.
- The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA.
- Department of Internal Medicine I, University Medical Center Schleswig-Holstein Campus, Kiel, Kiel, Germany.
- Institute of Clinical Molecular Biology, Christian-Albrecht-University of Kiel, Kiel, Germany; Department of Internal Medicine I, University Medical Center Schleswig-Holstein Campus, Kiel, Kiel, Germany.
- Department of General, Visceral, Thoracic, Vascular and Transplantation Surgery, University Medical Center Rostock, Rostock, Germany.
- Department of Dermatology and Allergy, University Hospital Schleswig-Holstein, Kiel, Germany.
- Institute of Microbiology, Infectious Diseases and Immunology, Gastrointestinal Microbiology Research Group, Charité - University Medicine Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
- Clinic for Conservative Dentistry and Periodontology, University Hospital Schleswig-Holstein, Campus, Kiel, Kiel, Germany.
- Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
- Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knoell Institute (HKI), Jena, Germany.
- Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knoell Institute (HKI), Jena, Germany; Friedrich Schiller Universität Jena, Jena, Germany.
- Department of Technical Immunology, Technische Universität Berlin, Berlin, Germany.
- Institute of Medical Immunology, Christian-Albrecht-University of Kiel, Kiel, Germany; Institute of Clinical Molecular Biology, Christian-Albrecht-University of Kiel, Kiel, Germany.
Abstract
The commensal yeast Candida albicans is a major inducer of human mucosal Th17 cells. How C. albicans drives Th17 cell responses at homeostasis, and whether such responses contribute to inflammatory diseases, remains poorly understood. Here, we showed that C. albicans-reactive Th17 cells targeted a limited set of proteins enriched in fungal extracellular vesicles. At homeostasis, these cells predominantly resided in the oral mucosa. However, T cell receptor profiling revealed shared clonotypes across oral and gut tissues, with C. albicans being a major driver of this repertoire overlap. In patients with Crohn's disease, C. albicans-specific Th17 cells with features of oral priming were enriched in intestinal tissues, where they retained their focused antigen specificity but acquired pathogenic Th17 cell traits. Together, our results reveal a stable, antigen-restricted C. albicans Th17 subset that is shared across mucosal sites and undergoes functional adaptation in the inflamed intestine. These cells represent a potential target for immune modulation in Crohn's disease.
MeSH
Cells, Mouth Mucosa, Homeostasis, Candida Albicans, Inflammatory Bowel Diseases, Immunity, Th17 Cells, Tissues, Mucous Membrane, Candida