| First Author | Kanamaru Y | Year | 2001 |
| Journal | J Immunol | Volume | 166 |
| Issue | 4 | Pages | 2818-23 |
| PubMed ID | 11160349 | Mgi Jnum | J:133192 |
| Mgi Id | MGI:3777909 | Doi | 10.4049/jimmunol.166.4.2818 |
| Citation | Kanamaru Y, et al. (2001) Blockade of TGF-beta signaling in T cells prevents the development of experimental glomerulonephritis. J Immunol 166(4):2818-23 |
| abstractText | Anti-glomerular basement membrane (GBM) Ab-induced glomerulonephritis (GN) at late stage is thought to be mediated by T cells. However, signaling pathways of T cells that are involved in the development of anti-GBM Ab-induced GN are unclear. We have recently established transgenic mice expressing Smad7, an inhibitor of TGF-beta signaling, in mature T cells, where signaling by TGF-beta was blocked specifically in T cells. In this study, we showed that anti-GBM Ab-induced GN was suppressed in several measures in the transgenic mice including the severity of glomerular changes, proteinuria, renal function, and CD4 T cell infiltration into the glomeruli without down-regulation of CD62 ligand (CD62L) (L-selectin) expression on CD4 T cells. Furthermore, treatment with the soluble fusion protein of CD62L and IgG enhanced anti-GBM Ab-induced GN. These findings indicated that blockade of TGF-beta signaling in T cells prevented the development of anti-GBM Ab-induced GN. Because CD62L on T cells appears to be inhibitory for the development of anti-GBM Ab-induced GN, persistent expression of CD62L on CD4 T cells may explain, at least in part, the suppression of anti-GBM Ab-induced GN in the transgenic mice. Our findings suggest that the development of anti-GBM Ab-induced GN requires TGF-beta/Smad signaling in T cells. |
