Viperin is required for optimal Th2 responses and T-cell receptor–mediated activation of NF-κB and AP-1
| Autor: | Keh-Chuang Chin, Peter Cresswell, Lian-Qun Qiu |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Transcriptional Activation
Ovalbumin JUNB medicine.medical_treatment Immunology Receptors Antigen T-Cell Mice Inbred Strains GATA3 Transcription Factor Biology Biochemistry Interferon-gamma Mice Th2 Cells Aldesleukin medicine Animals Cells Cultured Interleukin 4 T-cell receptor NF-kappa B GATA3 Proteins Cell Biology Hematology Mice Mutant Strains Cell biology Transcription Factor AP-1 Cytokine Immunoglobulin G Viperin Interleukin 13 Interleukin-4 Spleen Signal Transduction |
| Zdroj: | Blood. 113:3520-3529 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | 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-κB1/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-κB and AP-1 activities. |
| Databáze: | OpenAIRE |
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