Open AccessPD-1 cooperates with AIRE-mediated tolerance to prevent lethal autoimmune disease
Author(s) -
Antonia N. Policheni,
Charis E. Teh,
Alissa K. Robbins,
Selma Tuzlak,
Andreas Strasser
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2120149119
Subject(s) - peripheral tolerance , immune tolerance , autoimmune disease , immunology , central tolerance , regulator , immune system , autoimmunity , autoimmune regulator , self tolerance , function (biology) , biology , clonal deletion , microbiology and biotechnology , genetics , t cell receptor , t cell , gene , antibody
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.