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PD-1 and LAG-3 inhibitory co-receptors act synergistically to prevent autoimmunity in mice
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 lympho...
Autores principales: | , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039848/ https://www.ncbi.nlm.nih.gov/pubmed/21300912 http://dx.doi.org/10.1084/jem.20100466 |
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author | Okazaki, Taku Okazaki, Il-mi Wang, Jian Sugiura, Daisuke Nakaki, Fumio Yoshida, Taku Kato, Yu Fagarasan, Sidonia Muramatsu, Masamichi Eto, Tomoo Hioki, Kyoji Honjo, Tasuku |
author_facet | Okazaki, Taku Okazaki, Il-mi Wang, Jian Sugiura, Daisuke Nakaki, Fumio Yoshida, Taku Kato, Yu Fagarasan, Sidonia Muramatsu, Masamichi Eto, Tomoo Hioki, Kyoji Honjo, Tasuku |
author_sort | Okazaki, Taku |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-3039848 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-30398482011-08-14 PD-1 and LAG-3 inhibitory co-receptors act synergistically to prevent autoimmunity in mice Okazaki, Taku Okazaki, Il-mi Wang, Jian Sugiura, Daisuke Nakaki, Fumio Yoshida, Taku Kato, Yu Fagarasan, Sidonia Muramatsu, Masamichi Eto, Tomoo Hioki, Kyoji Honjo, Tasuku J Exp Med Article 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. The Rockefeller University Press 2011-02-14 /pmc/articles/PMC3039848/ /pubmed/21300912 http://dx.doi.org/10.1084/jem.20100466 Text en © 2011 Okazaki et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Article Okazaki, Taku Okazaki, Il-mi Wang, Jian Sugiura, Daisuke Nakaki, Fumio Yoshida, Taku Kato, Yu Fagarasan, Sidonia Muramatsu, Masamichi Eto, Tomoo Hioki, Kyoji Honjo, Tasuku PD-1 and LAG-3 inhibitory co-receptors act synergistically to prevent autoimmunity in mice |
title | PD-1 and LAG-3 inhibitory co-receptors act synergistically to prevent autoimmunity in mice |
title_full | PD-1 and LAG-3 inhibitory co-receptors act synergistically to prevent autoimmunity in mice |
title_fullStr | PD-1 and LAG-3 inhibitory co-receptors act synergistically to prevent autoimmunity in mice |
title_full_unstemmed | PD-1 and LAG-3 inhibitory co-receptors act synergistically to prevent autoimmunity in mice |
title_short | PD-1 and LAG-3 inhibitory co-receptors act synergistically to prevent autoimmunity in mice |
title_sort | pd-1 and lag-3 inhibitory co-receptors act synergistically to prevent autoimmunity in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039848/ https://www.ncbi.nlm.nih.gov/pubmed/21300912 http://dx.doi.org/10.1084/jem.20100466 |
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