TRIF signaling is essential for TLR4-driven IgE class switching
| dc.contributor.author | Janssen, Erin | |
| dc.contributor.author | Ozcan, Esra | |
| dc.contributor.author | Liadaki, Kyriaki | |
| dc.contributor.author | Jabara, Haifa H. | |
| dc.contributor.author | Manis, John | |
| dc.contributor.author | Ullas, Sumana | |
| dc.contributor.author | Akira, Shizuo | |
| dc.contributor.author | Fitzgerald, Katherine A. | |
| dc.contributor.author | Golenbock, Douglas T. | |
| dc.contributor.author | Geha, Raif S. | |
| dc.date | 2022-08-11T08:09:08.000 | |
| dc.date.accessioned | 2022-08-23T16:19:03Z | |
| dc.date.available | 2022-08-23T16:19:03Z | |
| dc.date.issued | 2014-03-15 | |
| dc.date.submitted | 2014-11-26 | |
| dc.identifier.citation | J Immunol. 2014 Mar 15;192(6):2651-8. doi: 10.4049/jimmunol.1300909. Epub 2014 Feb 14.<a href="http://dx.doi.org/10.4049/jimmunol.1300909">Link to article on publisher's site</a> | |
| dc.identifier.issn | 0022-1767 (Linking) | |
| dc.identifier.doi | 10.4049/jimmunol.1300909 | |
| dc.identifier.pmid | 24532577 | |
| dc.identifier.uri | http://hdl.handle.net/20.500.14038/34957 | |
| dc.description.abstract | 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-beta (TRIF)-related adaptor molecule (TRAM), which recruits TRIF. Following stimulation with LPS plus IL-4, Tram(-/-) and Trif(-/-) B cells completely failed to express Cepsilon germline transcripts (GLT) and secrete IgE. In contrast, Myd88(-/-) B cells had normal expression of Cepsilon GLT but reduced IgE secretion in response to LPS plus IL-4. Following LPS plus IL-4 stimulation, Cgamma1 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-kappaB p65 nuclear translocation beyond 3 h and had reduced binding of p65 to the Iepsilon promoter. Addition of the NF-kappaB inhibitor, JSH-23, to wild-type B cells 15 h after LPS plus IL-4 stimulation selectively blocked Cepsilon GLT expression and IgE secretion but had little effect on Cgamma1 GLT expression and IgG secretion. These results indicate that sustained activation of NF-kappaB driven by TRIF is essential for LPS plus IL-4-driven activation of the Cepsilon locus and class switching to IgE. | |
| dc.language.iso | en_US | |
| dc.relation | <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=24532577&dopt=Abstract">Link to Article in PubMed</a> | |
| dc.relation.url | http://dx.doi.org/10.4049/jimmunol.1300909 | |
| dc.subject | Adaptor Proteins, Vesicular Transport | |
| dc.subject | Animals | |
| dc.subject | B-Lymphocytes | |
| dc.subject | Cell Survival | |
| dc.subject | Cytidine Deaminase | |
| dc.subject | Immunoblotting | |
| dc.subject | Immunoglobulin Class Switching | |
| dc.subject | Immunoglobulin E | |
| dc.subject | Immunoglobulin G | |
| dc.subject | Immunoglobulin epsilon-Chains | |
| dc.subject | Immunoglobulin gamma-Chains | |
| dc.subject | Interleukin-4 | |
| dc.subject | Lipopolysaccharides | |
| dc.subject | Mice | |
| dc.subject | Mice, 129 Strain | |
| dc.subject | Mice, Inbred BALB C | |
| dc.subject | Mice, Inbred C57BL | |
| dc.subject | Mice, Knockout | |
| dc.subject | Myeloid Differentiation Factor 88 | |
| dc.subject | Phenylenediamines | |
| dc.subject | Receptors, Interleukin | |
| dc.subject | Reverse Transcriptase Polymerase Chain Reaction | |
| dc.subject | Signal Transduction | |
| dc.subject | Toll-Like Receptor 4 | |
| dc.subject | Transcription Factor RelA | |
| dc.subject | Cells | |
| dc.subject | Genetics | |
| dc.subject | Immunity | |
| dc.subject | Immunology and Infectious Disease | |
| dc.subject | Immunology of Infectious Disease | |
| dc.subject | Infectious Disease | |
| dc.title | TRIF signaling is essential for TLR4-driven IgE class switching | |
| dc.type | Journal Article | |
| dc.source.journaltitle | Journal of immunology (Baltimore, Md. : 1950) | |
| dc.source.volume | 192 | |
| dc.source.issue | 6 | |
| dc.identifier.legacycoverpage | https://escholarship.umassmed.edu/infdis_pp/179 | |
| dc.identifier.contextkey | 6399376 | |
| html.description.abstract | <p>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-beta (TRIF)-related adaptor molecule (TRAM), which recruits TRIF. Following stimulation with LPS plus IL-4, Tram(-/-) and Trif(-/-) B cells completely failed to express Cepsilon germline transcripts (GLT) and secrete IgE. In contrast, Myd88(-/-) B cells had normal expression of Cepsilon GLT but reduced IgE secretion in response to LPS plus IL-4. Following LPS plus IL-4 stimulation, Cgamma1 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-kappaB p65 nuclear translocation beyond 3 h and had reduced binding of p65 to the Iepsilon promoter. Addition of the NF-kappaB inhibitor, JSH-23, to wild-type B cells 15 h after LPS plus IL-4 stimulation selectively blocked Cepsilon GLT expression and IgE secretion but had little effect on Cgamma1 GLT expression and IgG secretion. These results indicate that sustained activation of NF-kappaB driven by TRIF is essential for LPS plus IL-4-driven activation of the Cepsilon locus and class switching to IgE.</p> | |
| dc.identifier.submissionpath | infdis_pp/179 | |
| dc.contributor.department | Department of Medicine, Division of Infectious Diseases and Immunology | |
| dc.source.pages | 2651-8 |
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