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タイトル: | Programmed cell death 1 inhibits inflammatory helper T-cell development through controlling the innate immune response |
著者: | Rui, Yuxiang Honjo, Tasuku Chikuma, Shunsuke |
著者名の別形: | 芮, 羽翔 本庶, 佑 竹馬, 俊介 |
キーワード: | autoimmunity inflammation |
発行日: | 16-Sep-2013 |
出版者: | National Academy of Sciences |
誌名: | Proceedings of the National Academy of Sciences of the United States of America |
巻: | 110 |
号: | 40 |
開始ページ: | 16073 |
終了ページ: | 16078 |
抄録: | Programmed cell death 1 (PD-1) is an inhibitory coreceptor on immune cells and is essential for self-tolerance because mice genetically lacking PD-1 (PD-1(-/-)) develop spontaneous autoimmune diseases. PD-1(-/-) mice are also susceptible to severe experimental autoimmune encephalomyelitis (EAE), characterized by a massive production of effector/memory T cells against myelin autoantigen, the mechanism of which is not fully understood. We found that an increased primary response of PD-1(-/-) mice to heat-killed mycobacteria (HKMTB), an adjuvant for EAE, contributed to the enhanced production of T-helper 17 (Th17) cells. Splenocytes from HKMTB-immunized, lymphocyte-deficient PD-1(-/-) recombination activating gene (RAG)2(-/-) mice were found to drive antigen-specific Th17 cell differentiation more efficiently than splenocytes from HKMTB-immunized PD-1(+/+) RAG2(-/-) mice. This result suggested PD-1's involvement in the regulation of innate immune responses. Mice reconstituted with PD-1(-/-) RAG2(-/-) bone marrow and PD-1(+/+) CD4(+) T cells developed more severe EAE compared with the ones reconstituted with PD-1(+/+) RAG2(-/-) bone marrow and PD-1(+/+) CD4(+) T cells. We found that upon recognition of HKMTB, CD11b(+) macrophages from PD-1(-/-) mice produced very high levels of IL-6, which helped promote naive CD4(+) T-cell differentiation into IL-17-producing cells. We propose a model in which PD-1 negatively regulates antimycobacterial responses by suppressing innate immune cells, which in turn prevents autoreactive T-cell priming and differentiation to inflammatory effector T cells. |
記述: | 免疫のブレーキPD-1が、自然免疫反応の調節によって免疫難病の発症を抑制することを解明. 京都大学プレスリリース. 2013-09-17. |
著作権等: | This is a postprint of the article, which has been published in final form at https://doi.org/10.1073/pnas.1315828110 この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。 This is not the published version. Please cite only the published version. |
URI: | http://hdl.handle.net/2433/178757 |
DOI(出版社版): | 10.1073/pnas.1315828110 |
PubMed ID: | 24043779 |
関連リンク: | https://www.kyoto-u.ac.jp/static/ja/news_data/h/h1/news6/2013/130917_2.htm |
出現コレクション: | 学術雑誌掲載論文等 |
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