TRIF signaling is essential for TLR4-driven IgE class switching
In: Journal of immunology (Baltimore, Md. : 1950), Jg. 192 (2014-02-18), Heft 6
Online
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Zugriff:
The TLR4 ligand LPS causes mouse B cells to undergo IgE and IgG1 isotype switching in the presence of IL-4. TLR4 activates two signaling pathways mediated by the adaptor molecules MyD88 and Toll/IL-IR domain-containing adapter-inducing IFN-β (TRIF)–related adaptor molecule (TRAM), which recruits TRIF. Following stimulation with LPS plus IL-4, Tram−/− and Trif−/− B cells completely failed to express Cε germline transcripts (GLT) and secrete IgE. In contrast, Myd88−/− B cells had normal expression of Cε GLT but reduced IgE secretion in response to LPS plus IL-4. Following LPS plus IL-4 stimulation, Cγ1 GLT expression was modestly reduced in Tram−/− and Trif−/− B cells, whereas Aicda expression and IgG1 secretion were reduced in Tram−/−, Trif−/−, and Myd88−/− B cells. B cells from all strains secreted normal amounts of IgE and IgG1 in response to anti-CD40 plus IL-4. Following stimulation with LPS plus IL-4, Trif−/− B cells failed to sustain NF-κB p65 nuclear translocation beyond 3 h and had reduced binding of p65 to the Iε promoter. Addition of the NF-κB inhibitor, JSH-23, to wild-type B cells 15 h after LPS plus IL-4 stimulation selectively blocked Cε GLT expression and IgE secretion but had little effect on Cγ1 GLT expression and IgG secretion. These results indicate that sustained activation of NF-κB driven by TRIF is essential for LPS plus IL-4–driven activation of the Cε locus and class switching to IgE.
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TRIF signaling is essential for TLR4-driven IgE class switching
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Autor/in / Beteiligte Person: | Akira, Shizuo ; Fitzgerald, Katherine A. ; Ozcan, Esra ; Geha, Raif S. ; Liadaki, Kyriaki ; Manis, John P. ; Ullas, Sumana ; Golenbock, Douglas T. ; Janssen, Erin ; Jabara, Haifa H. |
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Zeitschrift: | Journal of immunology (Baltimore, Md. : 1950), Jg. 192 (2014-02-18), Heft 6 |
Veröffentlichung: | 2014 |
Medientyp: | unknown |
ISSN: | 1550-6606 (print) |
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