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Intestinal cDC1 drive cross-tolerance to epithelial-derived antigen via induction of FoxP3+CD8+ Tregs.
Joeris, Thorsten; Gomez-Casado, Cristina; Holmkvist, Petra; Tavernier, Simon J; Silva-Sanchez, Aaron; Klotz, Luisa; Randall, Troy D; Mowat, Allan M; Kotarsky, Knut; Malissen, Bernard; Agace, William W.
Affiliation
  • Joeris T; Mucosal Immunology Group, Department of Health Technology, Technical University of Denmark, Kemitorvet, Kgs. Lyngby 2800, Denmark, Denmark.
  • Gomez-Casado C; Immunology Section, Lund University, Lund 221 84, Sweden.
  • Holmkvist P; Immunology Section, Lund University, Lund 221 84, Sweden.
  • Tavernier SJ; Immunology Section, Lund University, Lund 221 84, Sweden.
  • Silva-Sanchez A; Primary Immune Deficiency Research Laboratory, Department of Internal Diseases and Pediatrics, Centre for Primary Immunodeficiency Ghent, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Ghent 9000, Belgium.
  • Klotz L; VIB-UGent Center for Inflammation Research, Unit of Molecular Signal Transduction in Inflammation, 9000 Ghent, Belgium.
  • Randall TD; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
  • Mowat AM; University Hospital Münster, Department of Neurology with Institute of Translational Neurology, Münster 48149, Germany.
  • Kotarsky K; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
  • Malissen B; Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, Scotland.
  • Agace WW; Immunology Section, Lund University, Lund 221 84, Sweden.
Sci Immunol ; 6(60)2021 06 04.
Article in En | MEDLINE | ID: mdl-34088744
ABSTRACT
Although CD8+ T cell tolerance to tissue-specific antigen (TSA) is essential for host homeostasis, the mechanisms underlying peripheral cross-tolerance and whether they may differ between tissue sites remain to be fully elucidated. Here, we demonstrate that peripheral cross-tolerance to intestinal epithelial cell (IEC)-derived antigen involves the generation and suppressive function of FoxP3+CD8+ T cells. FoxP3+CD8+ Treg generation was dependent on intestinal cDC1, whose absence led to a break of tolerance and epithelial destruction. Mechanistically, intestinal cDC1-derived PD-L1, TGFß, and retinoic acid contributed to the generation of gut-tropic CCR9+CD103+FoxP3+CD8+ Tregs Last, CD103-deficient CD8+ T cells lacked tolerogenic activity in vivo, indicating a role for CD103 in FoxP3+CD8+ Treg function. Our results describe a role for FoxP3+CD8+ Tregs in cross-tolerance in the intestine for which development requires intestinal cDC1.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Dendritic Cells / T-Lymphocyte Subsets / T-Lymphocytes, Regulatory / CD8-Positive T-Lymphocytes / Peripheral Tolerance Limits: Animals Language: En Journal: Sci Immunol Year: 2021 Document type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Dendritic Cells / T-Lymphocyte Subsets / T-Lymphocytes, Regulatory / CD8-Positive T-Lymphocytes / Peripheral Tolerance Limits: Animals Language: En Journal: Sci Immunol Year: 2021 Document type: Article