Abstract:
:The key role of TRAF6 in TLR signaling pathways is well known. More recent evidence has implicated TRAF3 as another TRAF family member important to certain TLR responses of myeloid cells. Previous studies demonstrate that TRAF3 functions are highly context-dependent, displaying receptor and cell-type specificity. We thus examined the TLR responses of TRAF3(-/-)mouse B lymphocytes to test the hypothesis that TRAF3 plays distinct roles in such responses, depending on cell type. TRAF3(-/-) DC are known to have a defect in type 1 IFN production and here, showed diminished production of TNF and IL-10 and unaltered IL-6. In marked contrast, TRAF3(-/-) B cells made elevated amounts of TNF and IL-6 protein, as well as IL-10 and IP-10 mRNA, in response to TLR ligands. Also, in contrast to TRAF3(-/-) DC, the type 1 IFN pathway was elevated in TRAF3(-/-) B cells. Increased early responses of TRAF3(-/-) B cells to TLR signals were independent of cell survival or proliferation but associated with elevated canonical NF-κB activation. Additionally, TRAF3(-/-) B cells displayed enhanced TLR-mediated expression of AID and Ig isotype switching. Thus, TRAF3 plays varied and cell type-specific, biological roles in TLR responses.
journal_name
J Leukoc Bioljournal_title
Journal of leukocyte biologyauthors
Xie P,Poovassery J,Stunz LL,Smith SM,Schultz ML,Carlin LE,Bishop GAdoi
10.1189/jlb.0111044subject
Has Abstractpub_date
2011-12-01 00:00:00pages
1149-57issue
6eissn
0741-5400issn
1938-3673pii
jlb.0111044journal_volume
90pub_type
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