| First Author | Lai YG | Year | 2013 |
| Journal | Eur J Immunol | Volume | 43 |
| Issue | 9 | Pages | 2305-16 |
| PubMed ID | 23754237 | Mgi Jnum | J:201328 |
| Mgi Id | MGI:5513028 | Doi | 10.1002/eji.201243026 |
| Citation | Lai YG, et al. (2013) IL-15 modulates the balance between Bcl-2 and Bim via a Jak3/1-PI3K-Akt-ERK pathway to promote CD8alphaalpha(+) intestinal intraepithelial lymphocyte survival. Eur J Immunol 43(9):2305-16 |
| abstractText | IL-15 is an essential survival factor for CD8alphaalpha(+) intestinal intraepithelial lymphocytes (iIELs) in vitro and in vivo. However, the IL-15-induced survival signals in primary CD8alphaalpha(+) iIELs remains elusive. Although Bcl-2 level in CD8alphaalpha(+) iIELs positively correlates with IL-15Ralpha expression in the intestinal epithelial cells, overexpression of Bcl-2 only moderately restores CD8alphaalpha(+) gammadelta iIELs in Il15(-/-) mice. Here, we found that IL-15 promptly activated a Jak3-Jak1-PI3K-Akt pathway that led to the upregulation of Bcl-2 and Mcl-1. This pathway also induced a delayed but sustained ERK1/2 activation, which not only was necessary for the maintenance of Bcl-2 but also resulted in the phosphorylation of extra-long Bim at Ser(65) . The latter event facilitated the dissociation of Bim from Bcl-2 without affecting Bim abundance in IL-15-treated CD8alphaalpha(+) iIELs. Using an adoptive cell transfer approach, we found that either overexpression of Bcl-2 or removal of Bim from CD8alphaalpha(+) iIELs promoted their survival in Il15ra(-/-) mice. Taken together, IL-15 promotes CD8alphaalpha(+) iIEL survival by both increasing Bcl-2 levels and dissociating Bim from Bcl-2 through activation of a Jak3-Jak1-PI3K-Akt-ERK1/2 pathway, which differs from a previously reported IL-15-induced survival signal. |
