| RRC ID |
43477
|
| 著者 |
Diao H, Iwabuchi K, Li L, Onoe K, Van Kaer L, Kon S, Saito Y, Morimoto J, Denhardt DT, Rittling S, Uede T.
|
| タイトル |
Osteopontin regulates development and function of invariant natural killer T cells.
|
| ジャーナル |
Proc Natl Acad Sci U S A
|
| Abstract |
Invariant natural killer T (iNKT) cells belong to a subset of lymphocytes bridging innate and acquired immunity. We demonstrated that osteopontin (OPN) is involved in the activation of iNKT cells. In the present work, we examined whether OPN affects development and function of iNKT cells. We found that the number of peripheral iNKT cells was significantly reduced in OPN-deficient mice compared with wild-type mice. Although the number of thymic iNKT cells was not different between WT and OPN-deficient mice, intrathymic iNKT cell maturation was impaired in OPN-deficient mice. iNKT cell function was also significantly altered in OPN-deficient mice, as evidenced by (i) deficient down-regulation of iNKT cell receptor, (ii) reduction of IL-4 production while preserving production of IFN-gamma, and (iii) reduction of Fas ligand (FasL) expression, leading to reduced Fas/FasL-dependent cytotoxicity against hepatocytes. Importantly, activation of the transcription factors NFAT2 (nuclear factor of activated T cells 2) and GATA-3 was impaired, whereas activation of T-bet was preserved in iNKT cells of OPN-deficient mice. These data collectively indicate that OPN plays a pivotal role not only in the development, but also in the function of iNKT cells.
|
| 巻・号 |
105(41)
|
| ページ |
15884-9
|
| 公開日 |
2008-10-14
|
| DOI |
10.1073/pnas.0806089105
|
| PII |
0806089105
|
| PMID |
18836077
|
| PMC |
PMC2560993
|
| MeSH |
Animals
Down-Regulation
Fas Ligand Protein
Interleukin-4
Killer Cells, Natural / metabolism*
Killer Cells, Natural / physiology
Lymphocyte Activation*
Mice
Mice, Knockout
Osteopontin / deficiency
Osteopontin / physiology*
Receptors, KIR
Thymus Gland / immunology
Transcription Factors
|
| IF |
9.412
|
| 引用数 |
28
|
|
WOS 分野
|
IMMUNOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
|
