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*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Peripheral tolerance prevents autoimmune responses mediated by autoreactive T cells, and conventional dendritic cells (cDCs) can present tissue-specific antigen (TSA) and induce anergy and deletion of autoreactive T cells in local lymph nodes. Here, Joeris et al. examined the role of intestinal cDC1 presenting TSA derived from intestinal epithelial cells (IECs) in driving cross-tolerance of CD8+ T cells. cDC1 mediated peripheral tolerance by converting naïve CD8+ T cells to intestine-homing CCR9+ FoxP3+CD8+ Tregs, which involved programmed death ligand 1 (PD-L1), retinoic acid (RA), and transforming growth factor β (TGFβ) derived from intestinal cDC1. CD103 expression was needed for the tolerogenic function of these FoxP3+CD8+ Tregs. These findings highlight a role for cDC1-mediated induction of FoxP3+CD8+ Tregs in cross-tolerance to TSA in the intestine.
Original languageEnglish
Article numbereabd3774
JournalScience immunology
Volume6
Issue number16
Number of pages15
DOIs
Publication statusPublished - 2021

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