論文 - 詳細
| RRC ID | 89653 |
|---|---|
| 著者 | Wang Y, Koyama-Nasu R, Endo Y, Hasegawa I, Onodera A, Chen M, Hirahara K, Motohashi S, Nakayama T, Kimura MY. |
| タイトル | Distinct thymic pDC populations promote tumor immune tolerance through complementary mechanisms. |
| ジャーナル | Sci Adv |
| Abstract |
Thymic central tolerance is crucial for preventing autoimmunity, but its contribution to tumor immune evasion remains poorly understood. Here, we demonstrate that plasmacytoid dendritic cells (pDCs) in the thymus have two distinct subsets, accumulating in the thymus of tumor-bearing mice, contributing to immune tolerance through clonal deletion of tumor-specific T cells and reducing newly generated T cells. Mechanistically, common dendritic cell progenitor-derived pDCs (CDP-pDCs) capture tumor antigens and migrate to the thymus in a CCR9-dependent manner, where they present these antigens to induce clonal deletion of tumor-specific T cells. Concurrently, tumor progression inhibits T cell generation by promoting the accumulation of common lymphoid progenitor-derived pDCs (CLP-pDCs) within the thymus, which further produce type I interferon to alter thymic function. CCR9 deficiency prevents thymic accumulation of both pDCs, enhancing antitumor immunity and reducing tumor growth. Our findings reveal a previously unrecognized mechanism by which tumors hijack the physiological system to establish central tolerance against peripheral antigens, thereby promoting tolerance against themselves. |
| 巻・号 | 12(30) |
| ページ | eadx9864 |
| 公開日 | 2026-7-24 |
| DOI | 10.1126/sciadv.adx9864 |
| PMID | 42490439 |
| PMC | PMC13394480 |
| MeSH | Animals Antigens, Neoplasm / immunology Cell Movement Clonal Deletion Dendritic Cells* / immunology Dendritic Cells* / metabolism Immune Tolerance* Interferon Type I / metabolism Mice Mice, Knockout Neoplasms* / immunology Neoplasms* / pathology Receptors, CCR / genetics Receptors, CCR / metabolism T-Lymphocytes / immunology T-Lymphocytes / metabolism Thymus Gland* / cytology Thymus Gland* / immunology Thymus Gland* / pathology |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 21 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 38.2 |
| リソース情報 | |
| ヒト・動物細胞 | TSt-4/N-DLL1(RCB2120) |