Academic Journal
Dedicator of cytokinesis 8 regulates signal transducer and activator of transcription 3 activation and promotes TH17 cell differentiation
| العنوان: | Dedicator of cytokinesis 8 regulates signal transducer and activator of transcription 3 activation and promotes TH17 cell differentiation |
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| المؤلفون: | Charbonnier L.M., Keles S., Kabaleeswaran V., Reisli I., Genel F., Gulez N., Al-Herz W., Ramesh N., Perez-Atayde A., Karaca N.E., Kutukculer N., Wu H., Geha R.S., Chatila T.A. |
| بيانات النشر: | Mosby Inc. |
| سنة النشر: | 2016 |
| المجموعة: | Ege University Institutional Repository |
| مصطلحات موضوعية: | dedicator of cytokinesis 8, Cell division cycle 42, guanine nucleotide exchange factor, hyper-IgE syndrome, mucocutaneous candidiasis, suppressor of cytokine signaling 3, signal transducer and activator of transcription 3, TH17 |
| الوصف: | PubMed ID: 27350570 ; Background The autosomal recessive hyper-IgE syndrome (HIES) caused by dedicator of cytokinesis 8 (DOCK8) deficiency shares clinical features with autosomal dominant HIES because of signal transducer and activator of transcription 3 (STAT3) mutations, including recurrent infections and mucocutaneous candidiasis, which are suggestive of TH17 cell dysfunction. The mechanisms underlying this phenotypic overlap are unclear. Objective We sought to elucidate common mechanisms operating in the different forms of HIES. Methods We analyzed the differentiation of CD4+ TH cell subsets in control and DOCK8-deficient subjects. We also examined the role of DOCK8 in regulating STAT3 activation in T cells. TH cell differentiation was analyzed by ELISA, flow cytometry, and real-time PCR measurements of cytokines and TH cell transcription factors. The interaction of DOCK8 and STAT3 signaling pathways was examined by using flow cytometry, immunofluorescence, coimmunoprecipitation, and gene expression analysis. Results There was a profound block in the differentiation of DOCK8-deficient naive CD4+ T cells into TH17 cells. A missense mutation that disrupts DOCK8 guanine nucleotide exchange factor (GEF) activity while sparing protein expression also impaired TH17 cell differentiation. DOCK8 constitutively associated with STAT3 independent of GEF activity, whereas it regulated STAT3 phosphorylation in a GEF activity–dependent manner. DOCK8 also promoted STAT3 translocation to the nucleus and induction of STAT3-dependent gene expression. Conclusion DOCK8 interacts with STAT3 and regulates its activation and the outcome of STAT3-dependent TH17 differentiation. These findings might explain the phenotypic overlap between DOCK8 deficiency and autosomal dominant HIES. © 2016 American Academy of Allergy, Asthma ; Immunology |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0091-6749 |
| Relation: | Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı; Journal of Allergy and Clinical Immunology; https://hdl.handle.net/11454/25643; https://doi.org/10.1016/j.jaci.2016.04.023; 138; 1384; 1.39E+05 |
| DOI: | 10.1016/j.jaci.2016.04.023 |
| الاتاحة: | https://hdl.handle.net/11454/25643 https://doi.org/10.1016/j.jaci.2016.04.023 |
| Rights: | none |
| رقم الانضمام: | edsbas.535FFAC7 |
| قاعدة البيانات: | BASE |
| تدمد: | 00916749 |
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| DOI: | 10.1016/j.jaci.2016.04.023 |