Intestinal cDC1 drive cross-tolerance to epithelial-derived antigen via induction of FoxP3+CD8+ Tregs

Thorsten Joeris, Cristina Gomez-Casado, Petra Holmkvist, Simon J Tavernier, Aaron Silva-Sanchez, Luisa Klotz, Troy D Randall, Allan M Mowat, Knut Kotarsky, Bernard Malissen, William W Agace

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

Sammanfattning

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, TGFβ, 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.

Originalspråkengelska
Artikelnummereabd3774
TidskriftScience Immunology
Volym6
Nummer60
DOI
StatusPublished - 2021 juni

Ämnesklassifikation (UKÄ)

  • Immunologi inom det medicinska området
  • Cell- och molekylärbiologi

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