PD-1 cooperates with AIRE-mediated tolerance to prevent lethal autoimmune disease
- Author(s)
- Policheni, AN; Teh, CE; Robbins, A; Tuzlak, S; Strasser, A; Gray, DHD;
- Details
- Publication Year 2022-04-12,Volume 119,Issue #15,Page e2120149119
- Journal Title
- Proceedings of the National Academy of Sciences of the United States of America
- Abstract
- SignificanceA variety of mechanisms safeguard the body from autoimmune reactions, yet how these processes cooperate is largely unclear. Using a range of mouse genetic models, we uncover a critical tolerogenic axis between the autoimmune regulator, AIRE, and the immune checkpoint molecule, PD-1. Their combined loss induced an early-onset lethal autoimmune syndrome driven by autoreactive CD4(+) T cells that could not be restrained by regulatory T cells. These data shed light on how central and peripheral tolerance mechanisms work together, and highlight thymic function as a potentially key modifier of responses to anti-PD-1 therapies.
- Research Division(s)
- Immunology; Blood Cells And Blood Cancer
- PubMed ID
- 35394861
- Publisher's Version
- https://doi.org/10.1073/pnas.2120149119
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2022-04-11 11:15:11
Last Modified: 2022-04-11 11:22:04