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Essential Role for Caspase-8 in Toll-like Receptors and NFκB Signaling
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 cell...
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Published in: | The Journal of biological chemistry 2007-03, Vol.282 (10), p.7416 |
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Main Authors: | , , , , , , , , , , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
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Summary: | 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 IKKαβ,
and its loss resulted in delayed NFκB nuclear translocation and impaired NFκB 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 NFκB function. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M606721200 |