TRIF signaling is essential for TLR4-driven IgE class switching
| Autor: | Shizuo Akira, Katherine A. Fitzgerald, Esra Ozcan, Raif S. Geha, Kyriaki Liadaki, John P. Manis, Sumana Ullas, Douglas T. Golenbock, Erin Janssen, Haifa H. Jabara |
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| Rok vydání: | 2014 |
| Předmět: |
Lipopolysaccharides
Mice 129 Strain Cell Survival Immunoglobulin gamma-Chains Immunology Immunoblotting Phenylenediamines Immunoglobulin E Immunoglobulin G Article Mice Cytidine Deaminase Immunology and Allergy Animals Secretion Interleukin 4 Mice Knockout B-Lymphocytes Mice Inbred BALB C biology Reverse Transcriptase Polymerase Chain Reaction Transcription Factor RelA Receptors Interleukin Molecular biology Immunoglobulin Class Switching Mice Inbred C57BL Toll-Like Receptor 4 Adaptor Proteins Vesicular Transport Immunoglobulin class switching TRIF Myeloid Differentiation Factor 88 biology.protein TLR4 Immunoglobulin epsilon-Chains Interleukin-4 Signal transduction Signal Transduction |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 192(6) |
| ISSN: | 1550-6606 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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