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Novel process of intrathymic tumor-immune tolerance through CCR2-mediated recruitment of Sirpα + dendritic cells: A murine model
http://hdl.handle.net/2297/31956
http://hdl.handle.net/2297/31956b41776fd-aee1-40f5-b244-7af3eae0efc6
名前 / ファイル | ライセンス | アクション |
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CA-PR-BABA-T-41154.pdf (1.1 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2017-10-05 | |||||
タイトル | ||||||
タイトル | Novel process of intrathymic tumor-immune tolerance through CCR2-mediated recruitment of Sirpα + dendritic cells: A murine model | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Baba, Tomohisa
× Baba, Tomohisa× Badr, M.E.S.× Tomaru, Utano× Ishizu, Akihiro× Mukaida, Naofumi |
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書誌情報 |
PLoS ONE 巻 7, 号 7, p. e41154, 発行日 2012-07-16 |
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ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 1932-6203 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1371/journal.pone.0041154 | |||||
出版者 | ||||||
出版者 | Public Library of Science | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Immune surveillance system can detect more efficiently secretory tumor-specific antigens, which are superior as a target for cancer immunotherapy. On the contrary, immune tolerance can be induced in the thymus when a tumor antigen is massively secreted into circulation. Thus, the secretion of tumor-specific antigen may have contradictory roles in tumor immunity in a context-dependent manner. However, it remains elusive on the precise cellular mechanism of intrathymic immune tolerance against tumor antigens. We previously demonstrated that a minor thymic conventional dendritic cell (cDC) subset, CD8α -Sirpα + cDCs, but not the major subset, CD8α +Sirpα - cDCs can selectively capture blood-borne antigens and crucially contribute to the self-tolerance. In the present study, we further demonstrated that Sirpα + cDCs can capture a blood-borne antigen leaking inside the interlobular vascular-rich regions (IVRs). Blood-borne antigen selectively captured by Sirpα + cDCs can induce antigen-specific Treg generation or negative selection, depending on the immunogenicity of the presented antigen. Furthermore, CCR2 expression by thymic Sirpα + cDCs and abundant expression of its ligands, particularly, CCL2 by tumor-bearing mice prompted us to examine the function of thymic Sirpα + cDCs in tumor-bearing mice. Interestingly, tumor-bearing mice deposited CCL2 inside IVRs in the thymus. Moreover, tumor formation induced the accumulation of Sirpα + cDCs in IVRs under the control of CCR2-CCL2 axis and enhanced their capacity to take up antigens, resulting in the shift from Treg differentiation to negative selection. Finally, intrathymic negative selection similarly ensued in CCR2-competent mice once the tumor-specific antigen was secreted into bloodstream. Thus, we demonstrated that thymic Sirpα + cDCs crucially contribute to this novel process of intrathymic tumor immune tolerance. © 2012 Baba et al. | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
関連URI | ||||||
識別子タイプ | URI | |||||
関連識別子 | http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0041154 |