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Significance A 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… Click to show full abstract
Significance A 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.
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Year Published: 2022
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