Intestinal cDC1 drive cross-tolerance to epithelial-derived antigen via induction of FoxP3+CD8+ Tregs
(2021) In Science Immunology 6(60).- 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, TGFβ, and retinoic acid contributed to the generation of gut-tropic... (More)
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.
(Less)
- author
- organization
- publishing date
- 2021-06
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Science Immunology
- volume
- 6
- issue
- 60
- article number
- eabd3774
- publisher
- American Association for the Advancement of Science (AAAS)
- external identifiers
-
- scopus:85107535723
- pmid:34088744
- ISSN
- 2470-9468
- DOI
- 10.1126/sciimmunol.abd3774
- language
- English
- LU publication?
- yes
- id
- dd55cc66-71f2-428e-a7e6-fe9742c2a17b
- date added to LUP
- 2021-06-11 15:34:20
- date last changed
- 2024-09-07 20:29:09
@article{dd55cc66-71f2-428e-a7e6-fe9742c2a17b, abstract = {{<p>Although CD8<sup>+</sup> 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<sup>+</sup>CD8<sup>+</sup> T cells. FoxP3<sup>+</sup>CD8<sup>+</sup> T<sub>reg</sub> 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<sup>+</sup>CD103<sup>+</sup>FoxP3<sup>+</sup>CD8<sup>+</sup> T<sub>regs</sub>. Last, CD103-deficient CD8<sup>+</sup> T cells lacked tolerogenic activity in vivo, indicating a role for CD103 in FoxP3<sup>+</sup>CD8<sup>+</sup> T<sub>reg</sub> function. Our results describe a role for FoxP3<sup>+</sup>CD8<sup>+</sup> T<sub>regs</sub> in cross-tolerance in the intestine for which development requires intestinal cDC1.</p>}}, author = {{Joeris, Thorsten and Gomez-Casado, Cristina and Holmkvist, Petra and Tavernier, Simon J and Silva-Sanchez, Aaron and Klotz, Luisa and Randall, Troy D and Mowat, Allan M and Kotarsky, Knut and Malissen, Bernard and Agace, William W}}, issn = {{2470-9468}}, language = {{eng}}, number = {{60}}, publisher = {{American Association for the Advancement of Science (AAAS)}}, series = {{Science Immunology}}, title = {{Intestinal cDC1 drive cross-tolerance to epithelial-derived antigen via induction of FoxP3+CD8+ Tregs}}, url = {{http://dx.doi.org/10.1126/sciimmunol.abd3774}}, doi = {{10.1126/sciimmunol.abd3774}}, volume = {{6}}, year = {{2021}}, }