| First Author | Harada M | Year | 2006 |
| Journal | J Exp Med | Volume | 203 |
| Issue | 13 | Pages | 2929-37 |
| PubMed ID | 17178921 | Mgi Jnum | J:124812 |
| Mgi Id | MGI:3722564 | Doi | 10.1084/jem.20062206 |
| Citation | Harada M, et al. (2006) IL-21-induced Bepsilon cell apoptosis mediated by natural killer T cells suppresses IgE responses. J Exp Med 203(13):2929-37 |
| abstractText | Epidemiological studies have suggested that the recent increase in the incidence and severity of immunoglobulin (Ig)E-mediated allergic disorders is inversely correlated with Mycobacterium bovis bacillus Calmette Guerin (BCG) vaccination; however, the underlying mechanisms remain uncertain. Here, we demonstrate that natural killer T (NKT) cells in mice and humans play a crucial role in the BCG-induced suppression of IgE responses. BCG-activated murine Valpha14 NKT cells, but not conventional CD4 T cells, selectively express high levels of interleukin (IL)-21, which preferentially induces apoptosis in Bepsilon cells. Signaling from the IL-21 receptor increases the formation of a complex between Bcl-2 and the proapoptotic molecule Bcl-2-modifying factor, resulting in Bepsilon cell apoptosis. Similarly, BCG vaccination induces IL-21 expression by human peripheral blood mononuclear cells (PBMCs) in a partially NKT cell-dependent fashion. BCG-activated PBMCs significantly reduce IgE production by human B cells. These findings provide new insight into the therapeutic effect of BCG in allergic diseases. |
