| First Author | Chen Q | Year | 2019 |
| Journal | J Biol Chem | Volume | 294 |
| Issue | 14 | Pages | 5438-5455 |
| PubMed ID | 30745361 | Mgi Jnum | J:279578 |
| Mgi Id | MGI:6316383 | Doi | 10.1074/jbc.RA118.005418 |
| Citation | Chen Q, et al. (2019) alpha-Galactosylceramide treatment before allergen sensitization promotes iNKT cell-mediated induction of Treg cells, preventing Th2 cell responses in murine asthma. J Biol Chem 294(14):5438-5455 |
| abstractText | Asthma is a common inflammatory pulmonary disorder involving a diverse array of immune cells such as proinflammatory T helper 2 (Th2) cells. We recently reported that intraperitoneal injection of alpha-galactosylceramide (alpha-GalCer) can stimulate the lung invariant natural killer T (iNKT) cells and does not lead to airway inflammation in WT mice. Other studies indicate that iNKT cells play an important role in inducing regulatory T cells (Treg cells) and peripheral tolerance. Using iNKT cell- knockout mice, functional inactivation of Treg cells, and co-culture experiments in murine asthma models, we investigated the immunoregulatory effects of alpha-GalCer treatment before allergen sensitization on Th2 cell responses. We also studied whether alpha-GalCer's effects require lung Treg cells induced by activated iNKT cells. Our results disclosed that intraperitoneal administration of alpha-GalCer before allergen sensitization could promote the expansion and suppressive activity of lung CD4(+)FoxP3(+) Treg cells. These effects were accompanied by down-regulated Th2 cell responses and decreased immunogenic maturation of lung dendritic cells in WT mice. However, these changes were absent in CD1d(-/-) mice immunized and challenged with ovalbumin or house dust mites, indicating that the effects of alpha-GalCer on Treg cells mainly require iNKT cells. Moreover, functional inactivation of Treg cells could reverse the inhibitory ability of this alpha-GalCer therapy on Th2 cell responses in a murine asthma model. Our findings indicate that intraperitoneal administration of alpha-GalCer before the development of asthma symptoms induces the generation of lung Treg cells via iNKT cells and may provide a potential therapeutic strategy to prevent allergic asthma. |
