| First Author | Lemmers B | Year | 2007 |
| Journal | J Biol Chem | Volume | 282 |
| Issue | 10 | Pages | 7416-23 |
| PubMed ID | 17213198 | Mgi Jnum | J:120896 |
| Mgi Id | MGI:3708218 | Doi | 10.1074/jbc.M606721200 |
| Citation | Lemmers B, et al. (2007) Essential role for caspase-8 in Toll-like receptors and NFkappaB signaling. J Biol Chem 282(10):7416-23 |
| abstractText | In addition to its pro-apoptotic function in the death receptor pathway, roles for caspase-8 in mediating T-cell proliferation, maintaining lymphocyte homeostasis, and suppressing immunodeficiency have become evident. Humans with a germline point mutation of CASPASE-8 have multiple defects in T cells, B cells, and NK cells, most notably attenuated activation and immunodeficiency. By generating mice with B-cell-specific inactivation of caspase-8 (bcasp8(-/-)), we show that caspase-8 is dispensable for B-cell development, but its loss in B cells results in attenuated antibody production upon in vivo viral infection. We also report an important role for caspase-8 in maintaining B-cell survival following stimulation of the Toll-like receptor (TLR)2, -3, and -4. In response to TLR4 stimulation, caspase-8 is recruited to a complex containing IKKalphabeta, and its loss resulted in delayed NFkappaB nuclear translocation and impaired NFkappaB transcriptional activity. Our study supports dual roles for caspase-8 in apoptotic and nonapoptotic functions and demonstrates its requirement for TLR signaling and in the regulation of NFkappaB function. |
