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

ABSTRACT: 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.

SUBMITTER: Okazaki T

PROVIDER: S-EPMC3039848 | biostudies-other | 2011 Feb

REPOSITORIES: biostudies-other

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

Okazaki Taku T Okazaki Il-mi IM Wang Jian J Sugiura Daisuke D Nakaki Fumio F Yoshida Taku T Kato Yu Y Fagarasan Sidonia S Muramatsu Masamichi M Eto Tomoo T Hioki Kyoji K Honjo Tasuku T

The Journal of experimental medicine 20110207 2

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 mic ...[more]

PMID: 21300912

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