Viperin is required for optimal Th2 responses and T-cell receptor-mediated activation of NF-kappaB and AP-1.
Viperin (virus inhibitory protein, endoplasmic reticulum [ER]-associated, interferon-inducible) has been identified as a highly inducible ER protein that has antiviral activity. Here, we characterized the phenotype of mice deficient in viperin and examined the biological function of viperin in peripheral T-cell activation and differentiation. Splenic CD4(+) T cells deficient in viperin exhibited normal anti-T-cell receptor (TCR)-induced proliferation and IL-2 production, but produced significantly less T helper 2 (Th2) cytokines, including IL-4, IL-5, and IL-13, in association with impaired GATA3 activation, after stimulation with anti-CD3 antibody, which was not restored upon costimulation with anti-CD28. Th2 differentiation of viperin-deficient naive T cells was also impaired in the presence of strong TCR signaling and minimum IL-4, but not under optimal Th2-skewed conditions. In parallel, viperin-deficient T cells showed decreases in NF-kappaB1/p50 and AP-1/JunB DNA binding activities after TCR engagement. Thus, viperin facilitates TCR-mediated GATA-3 activation and optimal Th2 cytokine production by modulating NF-kappaB and AP-1 activities.
Qiu
Lian-Qun
LQ
Laboratory of Gene Regulation and Inflammation, Singapore Immunology Network, Biomedical Sciences Institutes, Singapore.
Cresswell
Peter
P
Chin
Keh-Chuang
KC
D000818:Animals; D002478:Cells, Cultured; D050990:GATA3 Transcription Factor / Q000378:metabolism; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D016328:NF-kappa B / Q000378:metabolism*; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013154:Spleen / Q000166:cytology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D015533:Transcriptional Activation / Q000276:immunology; D000090123:Viperin Protein
D050990:GATA3 Transcription Factor; D007074:Immunoglobulin G; D007371:Interferon-gamma; D015847:Interleukin-4; D016328:NF-kappa B; D010047:Ovalbumin; D011506:Proteins; D011948:Receptors, Antigen, T-Cell; D018808:Transcription Factor AP-1; C494748:Gata3 protein, mouse; C417529:Rsad2 protein, mouse; D000090123:Viperin Protein