دورية أكاديمية
The transcriptional activator Gli2 modulates T-cell receptor signalling through attenuation of AP-1 and NFκB activity
| العنوان: | The transcriptional activator Gli2 modulates T-cell receptor signalling through attenuation of AP-1 and NFκB activity |
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| المؤلفون: | Furmanski, Anna L., Barbarulo, Alessandro, Solanki, Anisha, Lau, Ching-In, Sahni, Hemant, Saldaña, José Ignacio, D’Acquisto, Fulvio, Crompton, Tessa |
| المساهمون: | University College London, QMUL, University of Bedfordshire |
| بيانات النشر: | The Company of Biologists Ltd |
| سنة النشر: | 2015 |
| المجموعة: | University of Bedfordshire Repository |
| مصطلحات موضوعية: | Hedgehog, Gli2, T-cell, TCR, AP-1, NFκB, IL-2, transcription, cell science, C130 Cell Biology |
| الوصف: | Different tissues contain diverse and dynamic cellular niches, providing distinct signals to tissue-resident or migratory infiltrating immune cells. Hedgehog (Hh) proteins are secreted inter-cellular signalling molecules, which are essential during development and are important in cancer, post-natal tissue homeostasis and repair. Hh signalling mediated by the Hh-responsive transcription factor Gli2 also has multiple roles in T-lymphocyte development and differentiation.Here, we investigate the function of Gli2 in T-cell signalling and activation. Gene transcription driven by the Gli2 transcriptional activator isoform (Gli2A) attenuated T-cell activation and proliferation following T-cell receptor (TCR) stimulation. Expression of Gli2A in T-cells altered gene expression profiles, impaired the TCR-induced Ca2+ flux and nuclear expression of NFAT2, suppressed upregulation of molecules essential for activation, and attenuated signalling pathways upstream of the AP-1 and NFκB complexes, leading to reduced activation of these important transcription factors. Inhibition of physiological Hh-dependent transcription increased NFκB activity upon TCR ligation. These data are important for nderstanding the molecular mechanisms of immunomodulation, particularly in tissues where Hh proteins or other Gli-activating ligands such as TGFβ are upregulated, including during inflammation, tissue damage and repair, and in tumour microenvironments. ; Biotechnology and Biological Sciences Research Council (BBSRC) [grant number BBSRC BB/I026324/1]; and the UK Medical Research Council (MRC) [grant number MRC G0900161]. A.L.F is supported by Asthma UK [grant number AUK-SPD-2012- 171]. H.S. was supported by a Child Health Research (CHR) studentship, A.B. by Istituto Pasteur/Cenci Bolognetti and A.S and T.C by Great Ormond Street Children's Charity (GOSHCC). Deposited in PMC for immediate release. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1477-9137 0021-9533 |
| العلاقة: | https://jcs.biologists.org/content/128/11/2085.article-infoTest; Furmanski AL, Barbarulo A, Solanki A, Lau CI, Sahni H, Saldana JI, D’Acquisto F & Crompton T, (2015) 'The transcriptional activator Gli2 modulates T-cell receptor signalling through attenuation of AP-1 and NFκ-B activity', Journal of Cell Science. Vol 128, pp 2085-2095; http://hdl.handle.net/10547/576908Test; Journal of Cell Science; PMC4450292 |
| DOI: | 10.1242/jcs.165803 |
| الإتاحة: | https://doi.org/10.1242/jcs.165803Test http://hdl.handle.net/10547/576908Test |
| رقم الانضمام: | edsbas.76612DB6 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 14779137 00219533 |
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| DOI: | 10.1242/jcs.165803 |