2009 Fiscal Year Final Research Report
Tolerance induction of apoptotic cell-associated antigens by antigen presenting cells.
| 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
|
| Keywords | 細胞 |
|---|
| 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.
|
-
[Journal Article] xCT deficiency accelerates chemically induced tumorigenesis.2010
Author(s)
Nabeyama A, Kurita A, Asano K, Miyake Y, Yasuda T, Miura I, Nishitai G, Arakawa S, Shimizu S, Wakana S, Yoshida H, Tanaka M
-
Journal Title
Proc Natl Acad Sci U S A 107
Pages: 6436-6441
Peer Reviewed
-
[Journal Article] Novel subset of CD8+ dendritic cells localized in the marginal zone is responsible for tolerance to cell-associated antigens.2009
Author(s)
Qiu, CH*, Miyake, Y*., Kaise, H., Kitamura, H., Ohara, O., Tanaka, M.
-
Journal Title
J. Immunol. 182
Pages: 4127-4136
Peer Reviewed
-
-
-
-
