Project/Area Number |
20790312
|
Research Category |
Grant-in-Aid for Young Scientists (B)
|
Allocation Type | Single-year Grants |
Research Field |
Experimental pathology
|
Research Institution | The Institute of Physical and Chemical Research |
Principal Investigator |
MIYAKE Yasunobu The Institute of Physical and Chemical Research, 生体防御医学研究所・分子免疫学分野, 助教 (10392143)
|
Project Period (FY) |
2008 – 2009
|
Project Status |
Completed (Fiscal Year 2009)
|
Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
Keywords | 細胞 / 死細胞貪食 / 樹状細胞 / 免疫寛容 |
Research Abstract |
Apoptotic cell clearance by dendritic cells (DCs) plays a crucial role in the maintenance of self-tolerance. In spleen, CD8α+ DCs are thought to be responsible for this phenomenon by phagocytosing circulating apoptotic cells. However, as CD8α+ DCs are believed to be predominantly localized in the T cell zone, it remains unclear how these DCs phagocytose blood-borne apoptotic cells accumulated in the marginal zone (MZ). In this study, we identified a subpopulation of CD8α+ DCs responsible for tolerance induction to cell-associated Ags. Among splenic CD8α+ DCs, the CD103+, CD207+ subset was preferentially localized in the MZ and dominantly phagocytosed blood-borne apoptotic cells. After phagocytosis of apoptotic cells, this DC subset migrated into the T cell zone for cross-presentation of cell-associated Ags. Stimulation of TLRs induced the disappearance of this DC subset. Consequently, CD8α+ DCs neither phagocytosed injected apoptotic cells nor presented cell-associated Ags in mice treated with TLR ligands. Transient ablation of this DC subset by cytochrome c injection resulted in a failure of tolerance induction to cell-associated Ags, indicating that this DC subset is essential for tolerance induction by apoptotic cell clearance.
|