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

doi:10.1126/sciimmunol.abd3774

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

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 journal › Journal article › Research › peer-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+ Tr_egs, 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+ T_regs. These findings highlight a role for cDC1-mediated induction of FoxP3+CD8+ T_regs in cross-tolerance to TSA in the intestine.

Original language	English
Article number	eabd3774
Journal	Science immunology
Volume	6
Issue number	16
Number of pages	15
DOIs	https://doi.org/10.1126/sciimmunol.abd3774
Publication status	Published - 2021

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@article{aba5c166c20f472dbee36126abba84c3,

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

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 na{\"i}ve 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.",

author = "Thorsten Joeris and Cristina Gomez-Casado and Petra Holmkvist and Tavernier, \{Simon J.\} and Aaron Silva-Sanchez and Luisa Klotz and Randall, \{Troy D.\} and Mowat, \{Allan M.\} and Knut Kotarsky and Bernard Malissen and Agace, \{William W.\}",

year = "2021",

doi = "10.1126/sciimmunol.abd3774",

language = "English",

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journal = "Science immunology",

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publisher = "American Association for the Advancement of Science",

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T1 - Intestinal cDC1 drive cross-tolerance to epithelial-derived antigen via induction of FoxP3+CD8+ Tregs

AU - Joeris, Thorsten

AU - Gomez-Casado, Cristina

AU - Holmkvist, Petra

AU - Tavernier, Simon J.

AU - Silva-Sanchez, Aaron

AU - Klotz, Luisa

AU - Randall, Troy D.

AU - Mowat, Allan M.

AU - Kotarsky, Knut

AU - Malissen, Bernard

AU - Agace, William W.

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

U2 - 10.1126/sciimmunol.abd3774

DO - 10.1126/sciimmunol.abd3774

M3 - Journal article

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SN - 2470-9468

VL - 6

JO - Science immunology

JF - Science immunology

IS - 16

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