| First Author | Pankewycz O | Year | 2012 |
| Journal | Eur J Immunol | Volume | 42 |
| Issue | 9 | Pages | 2409-18 |
| PubMed ID | 22674044 | Mgi Jnum | J:187949 |
| Mgi Id | MGI:5438767 | Doi | 10.1002/eji.201141533 |
| Citation | Pankewycz O, et al. (2012) Inhibiting Wipf2 downregulation by transgenic expression of its 3' mRNA-untranslated region improves cytotoxicity and vaccination response. Eur J Immunol 42(9):2409-18 |
| abstractText | Lymphocyte activation results in profound changes in the abundance of mRNA transcripts many of which are downregulated. The Wiskott-Aldrich syndrome (WAS) protein (WASP) family is critical for productive T-cell receptor signaling and actin reorganization. The WASP signal pathway includes the WAS/WAS-like (WASL) interacting protein family 2 (WIPF2) gene also known as WIRE/WICH. We show that both human WIPF2 and mouse Wipf2 are mice, alternatively spliced within the 3' untranslated region (3'UTR) resulting in two major transcripts of approximately 4.5 and 6 kb in size. Following T-cell activation, the level of human WIPF2 and mouse Wipf2 mRNA rapidly declines. In mice, this decline is accompanied by a marked reduction in WIPF2 protein levels. Transgenic expression of a 240-bp fragment derived from a highly conserved terminal 3'UTR found within the 6-kb transcript blocks Wipf2 downregulation. These effects may be mediated by competitive inhibition of microinhibitory RNA (miRNA) regulation since the 6-kb-derived transgene and the 4.5-kb transcript share functional binding sites for miRNA146a. Blocking Wipf2 gene and protein repression resulted in improved T-cell responses to antigen immunization in vivo as well as in vitro cytotoxic T-cell killing. Collectively, these data suggest that early downregulation of this immunologically relevant gene controls the intensity of selective lymphocyte functions. |
