5 results on '"William E. Hughes"'
Search Results
2. IL-21 restricts T follicular regulatory T cell proliferation through Bcl-6 mediated inhibition of responsiveness to IL-2
- Author
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Christoph Jandl, Sue M. Liu, Pablo F. Cañete, Joanna Warren, William E. Hughes, Alexis Vogelzang, Kylie Webster, Maria E. Craig, Gulbu Uzel, Alexander Dent, Polina Stepensky, Bärbel Keller, Klaus Warnatz, Jonathan Sprent, and Cecile King
- Subjects
Science - Abstract
IL-21 is central to follicular helper T cell function and germinal centre responses. Here the authors show that IL-21 signalling directly inhibits T follicular regulatory cells by limiting Bcl-6-dependent IL-2 receptor expression.
- Published
- 2017
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3. Peripheral-specific Y1 receptor antagonism increases thermogenesis and protects against diet-induced obesity
- Author
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Ronaldo F. Enriquez, Chi Kin Ip, Luoning Gou, Paul Timpson, Zefeng Xia, Tianshu Zeng, Max Nobis, Qiao-Ping Wang, William E. Hughes, Kailun Lee, Jackie Lau, Hanyu Gao, Qi Wu, Chenxu Yan, Herbert Herzog, D. Ross Laybutt, Mohammed Bensellam, Lei Zhang, Yan-Chuan Shi, Jody J. Haigh, Zhongmin Gao, Kim Loh, and UCL - SSS/IREC/EDIN - Pôle d'endocrinologie, diabète et nutrition
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Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Science ,Biopsy ,Primary Cell Culture ,General Physics and Astronomy ,030209 endocrinology & metabolism ,White adipose tissue ,Carbohydrate metabolism ,Arginine ,Diet, High-Fat ,General Biochemistry, Genetics and Molecular Biology ,Energy homeostasis ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Adipose Tissue, Brown ,Internal medicine ,Brown adipose tissue ,Adipocytes ,medicine ,Animals ,Humans ,Glucose homeostasis ,Obesity ,Cells, Cultured ,Multidisciplinary ,Chemistry ,Thermogenesis ,General Chemistry ,Middle Aged ,Neuropeptide Y receptor ,Receptors, Neuropeptide Y ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Female ,Energy Metabolism ,Antagonism - Abstract
Obesity is caused by an imbalance between food intake and energy expenditure (EE). Here we identify a conserved pathway that links signalling through peripheral Y1 receptors (Y1R) to the control of EE. Selective antagonism of peripheral Y1R, via the non-brain penetrable antagonist BIBO3304, leads to a significant reduction in body weight gain due to enhanced EE thereby reducing fat mass. Specifically thermogenesis in brown adipose tissue (BAT) due to elevated UCP1 is enhanced accompanied by extensive browning of white adipose tissue both in mice and humans. Importantly, selective ablation of Y1R from adipocytes protects against diet-induced obesity. Furthermore, peripheral specific Y1R antagonism also improves glucose homeostasis mainly driven by dynamic changes in Akt activity in BAT. Together, these data suggest that selective peripheral only Y1R antagonism via BIBO3304, or a functional analogue, could be developed as a safer and more effective treatment option to mitigate diet-induced obesity. Neuropeptide Y signalling in the periphery contributes to the regulation of metabolic and energy homeostasis. Here the authors show that blocking Y1R signalling in peripheral tissues using the selective antagonist BIBO3304 ameliorates diet-induced obesity and improves whole-body glucose metabolism.
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- 2021
4. Live imaging molecular changes in junctional tension upon VE-cadherin in zebrafish
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William E. Hughes, Daniel E. Conway, Benjamin M. Hogan, Markus Affolter, Daniel Hesselson, Kelly A. Smith, Anne K. Lagendijk, Scott Paterson, Sungmin Baek, Guillermo A. Gomez, Heinz-Georg Belting, Martin A. Schwartz, Alpha S. Yap, Lagendijk, Anne Karine, Gomez, Guillermo A, Baek, Sungmin, Hesselson, Daniel, Hughes, William E, Paterson, Scott, Conway, Daniel E, Belting, Heinz-Georg, Affolter, Markus, Smith, Kelly A, Schwartz, Martin A, Yap, Alpha S, and Hogan, Benjamin M
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0301 basic medicine ,Science ,General Physics and Astronomy ,Neovascularization, Physiologic ,macromolecular substances ,Cell junction ,Mechanotransduction, Cellular ,General Biochemistry, Genetics and Molecular Biology ,Article ,Contractility ,angiogenesis ,03 medical and health sciences ,Dorsal aorta ,Live cell imaging ,Antigens, CD ,Tensile Strength ,Fluorescence Resonance Energy Transfer ,Animals ,Mechanotransduction ,lcsh:Science ,Zebrafish ,Aorta ,mechanotransduction ,Multidisciplinary ,biology ,Cadherin ,General Chemistry ,Actomyosin ,Zebrafish Proteins ,biology.organism_classification ,Cadherins ,Cell biology ,Biomechanical Phenomena ,Molecular Imaging ,030104 developmental biology ,Intercellular Junctions ,Mutation ,lcsh:Q ,VE-cadherin ,cadherins - Abstract
Forces play diverse roles in vascular development, homeostasis and disease. VE-cadherin at endothelial cell-cell junctions links the contractile acto-myosin cytoskeletons of adjacent cells, serving as a tension-transducer. To explore tensile changes across VE-cadherin in live zebrafish, we tailored an optical biosensor approach, originally established in vitro. We validate localization and function of a VE-cadherin tension sensor (TS) in vivo. Changes in tension across VE-cadherin observed using ratio-metric or lifetime FRET measurements reflect acto-myosin contractility within endothelial cells. Furthermore, we apply the TS to reveal biologically relevant changes in VE-cadherin tension that occur as the dorsal aorta matures and upon genetic and chemical perturbations during embryonic development., Mechanical forces play a crucial role during morphogenesis, but how these are sensed and transduced in vivo is not fully understood. Here the authors apply a FRET tension sensor to live zebrafish and study changes in VE-cadherin tension at endothelial cell-cell junctions during arterial maturation.
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- 2017
5. IL-21 restricts T follicular regulatory T cell proliferation through Bcl-6 mediated inhibition of responsiveness to IL-2
- Author
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Klaus Warnatz, Alexander L. Dent, Polina Stepensky, William E. Hughes, Maria E. Craig, Pablo F. Canete, Joanna Warren, Sue M. Liu, Christoph Jandl, Kylie E. Webster, Jonathan Sprent, Cecile King, Alexis Vogelzang, Bärbel Keller, and Gulbu Uzel
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Male ,0301 basic medicine ,Interleukin 2 ,Receptors, CXCR4 ,endocrine system ,Adolescent ,Regulatory T cell ,Science ,General Physics and Astronomy ,T-Lymphocytes, Regulatory ,Article ,General Biochemistry, Genetics and Molecular Biology ,Mice ,03 medical and health sciences ,Interleukin 21 ,0302 clinical medicine ,medicine ,Animals ,Humans ,Cytotoxic T cell ,IL-2 receptor ,Child ,Cell Proliferation ,Mice, Knockout ,Multidisciplinary ,biology ,Chemistry ,Interleukins ,Immunologic Deficiency Syndromes ,Infant ,Interleukin-21 Receptor alpha Subunit ,Interleukin ,FOXP3 ,General Chemistry ,Immunity, Humoral ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Proto-Oncogene Proteins c-bcl-6 ,biology.protein ,Interleukin-2 ,Female ,Antibody ,030215 immunology ,medicine.drug - Abstract
T follicular regulatory (Tfr) cells control the magnitude and specificity of the germinal centre reaction, but how regulation is contained to ensure generation of high-affinity antibody is unknown. Here we show that this balance is maintained by the reciprocal influence of interleukin (IL)-2 and IL-21. The number of IL-2-dependent FoxP3+ regulatory T cells is increased in the peripheral blood of human patients with loss-of-function mutations in the IL-21 receptor (IL-21R). In mice, IL-21:IL-21R interactions influence the phenotype of T follicular cells, reducing the expression of CXCR4 and inhibiting the expansion of Tfr cells after T-cell-dependent immunization. The negative effect of IL-21 on Tfr cells in mice is cell intrinsic and associated with decreased expression of the high affinity IL-2 receptor (CD25). Bcl-6, expressed in abundance in Tfr cells, inhibits CD25 expression and IL-21-mediated inhibition of CD25 is Bcl-6 dependent. These findings identify a mechanism by which IL-21 reinforces humoral immunity by restricting Tfr cell proliferation., IL-21 is central to follicular helper T cell function and germinal centre responses. Here the authors show that IL-21 signalling directly inhibits T follicular regulatory cells by limiting Bcl-6-dependent IL-2 receptor expression.
- Published
- 2017
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