PD-1 and LAG-3 inhibitory co-receptors act synergistically to prevent autoimmunity in mice

  • Okazaki T
  • Okazaki I
  • Wang J
 et al. 
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Stimulatory and inhibitory co-receptors play fundamental roles in the regulation of the immune system. We describe a new mouse model of spontaneous autoimmune disease. Activation-induced cytidine deaminase-linked autoimmunity (aida) mice harbor a loss-of-function mutation in the gene encoding lymphocyte activation gene 3 (LAG-3), an inhibitory co-receptor. Although LAG-3 deficiency alone did not induce autoimmunity in nonautoimmune-prone mouse strains, it induced lethal myocarditis in BALB/c mice deficient for the gene encoding the inhibitory co-receptor programmed cell death 1 (PD-1). In addition, LAG-3 deficiency alone accelerated type 1 diabetes mellitus in nonobese diabetic mice. These results demonstrate that LAG-3 acts synergistically with PD-1 and/or other immunoregulatory genes to prevent autoimmunity in mice.

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  • Taku Okazaki

  • Il-mi Okazaki

  • Jian Wang

  • Daisuke Sugiura

  • Fumio Nakaki

  • Taku Yoshida

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