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Start Over Author "Lucy, S" Journal nature communications
16 results on '"Lucy, S"'

1. CTLA-4 expressing innate lymphoid cells modulate mucosal homeostasis in a microbiota dependent manner

Author

Jonathan W. Lo, Jan-Hendrik Schroeder, Luke B. Roberts, Rami Mohamed, Domenico Cozzetto, Gordon Beattie, Omer S. Omer, Ellen M. Ross, Frank Heuts, Geraldine M. Jowett, Emily Read, Matthew Madgwick, Joana F. Neves, Tamas Korcsmaros, Richard G. Jenner, Lucy S. K. Walker, Nick Powell, and Graham M. Lord

Subjects
Science
Abstract

Abstract The maintenance of intestinal homeostasis is a fundamental process critical for organismal integrity. Sitting at the interface of the gut microbiome and mucosal immunity, adaptive and innate lymphoid populations regulate the balance between commensal micro-organisms and pathogens. Checkpoint inhibitors, particularly those targeting the CTLA-4 pathway, disrupt this fine balance and can lead to inflammatory bowel disease and immune checkpoint colitis. Here, we show that CTLA-4 is expressed by innate lymphoid cells and that its expression is regulated by ILC subset-specific cytokine cues in a microbiota-dependent manner. Genetic deletion or antibody blockade of CTLA-4 in multiple in vivo models of colitis demonstrates that this pathway plays a key role in intestinal homeostasis. Lastly, we have found that this observation is conserved in human IBD. We propose that this population of CTLA-4-positive ILC may serve as an important target for the treatment of idiopathic and iatrogenic intestinal inflammation.

Published
2024
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4. Cortical depth profiles in primary visual cortex for illusory and imaginary experiences

Author

Johanna Bergmann, Lucy S. Petro, Clement Abbatecola, Min S. Li, A. Tyler Morgan, and Lars Muckli

Subjects
Science
Abstract

Abstract Visual illusions and mental imagery are non-physical sensory experiences that involve cortical feedback processing in the primary visual cortex. Using laminar functional magnetic resonance imaging (fMRI) in two studies, we investigate if information about these internal experiences is visible in the activation patterns of different layers of primary visual cortex (V1). We find that imagery content is decodable mainly from deep layers of V1, whereas seemingly ‘real’ illusory content is decodable mainly from superficial layers. Furthermore, illusory content shares information with perceptual content, whilst imagery content does not generalise to illusory or perceptual information. Together, our results suggest that illusions and imagery, which differ immensely in their subjective experiences, also involve partially distinct early visual microcircuits. However, overlapping microcircuit recruitment might emerge based on the nuanced nature of subjective conscious experience.

Published
2024
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6. Costimulation blockade in combination with IL-2 permits regulatory T cell sparing immunomodulation that inhibits autoimmunity

Author

Chun Jing Wang, Lina Petersone, Natalie M. Edner, Frank Heuts, Vitalijs Ovcinnikovs, Elisavet Ntavli, Alexandros Kogimtzis, Astrid Fabri, Yassin Elfaki, Luke P. Houghton, Ralf J. Hosse, David A. Schubert, Andreas P. Frei, Ellen M. Ross, and Lucy S. K. Walker

Subjects
Science
Abstract

Abstract Blockade of CD28 costimulation with CTLA-4-Ig/Abatacept is used to dampen effector T cell responses in autoimmune and transplantation settings. However, a significant drawback of this approach is impaired regulatory T cell homeostasis that requires CD28 signaling. Therefore, strategies that restrict the effects of costimulation blockade to effector T cells would be advantageous. Here we probe the relative roles of CD28 and IL-2 in maintaining Treg. We find provision of IL-2 counteracts the regulatory T cell loss induced by costimulation blockade while minimally affecting the conventional T cell compartment. These data suggest that combining costimulation blockade with IL-2 treatment may selectively impair effector T cell responses while maintaining regulatory T cells. Using a mouse model of autoimmune diabetes, we show combined therapy supports regulatory T cell homeostasis and protects from disease. These findings are recapitulated in humanised mice using clinically relevant reagents and provide an exemplar for rational use of a second immunotherapy to offset known limitations of the first.

Published
2022
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10. Protease-controlled secretion and display of intercellular signals

Author

Alexander E. Vlahos, Jeewoo Kang, Carlos A. Aldrete, Ronghui Zhu, Lucy S. Chong, Michael B. Elowitz, and Xiaojing J. Gao

Subjects
Science
Abstract

To program intercellular communication for biomedicine, it is crucial to regulate the secretion and surface display of signaling proteins. Here the authors develop RELEASE, a modular approach to control intercellular signals using protein-based circuits.

Published
2022
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11. Genomic profile of advanced breast cancer in circulating tumour DNA

Author

Belinda Kingston, Rosalind J. Cutts, Hannah Bye, Matthew Beaney, Giselle Walsh-Crestani, Sarah Hrebien, Claire Swift, Lucy S. Kilburn, Sarah Kernaghan, Laura Moretti, Katie Wilkinson, Andrew M. Wardley, Iain R. Macpherson, Richard D. Baird, Rebecca Roylance, Jorge S. Reis-Filho, Michael Hubank, Iris Faull, Kimberly C. Banks, Richard B. Lanman, Isaac Garcia-Murillas, Judith M. Bliss, Alistair Ring, and Nicholas C. Turner

Subjects
Science
Abstract

Circulating tumour DNA can provide useful information on disease burden. Here, the authors analysed circulating tumour DNA from 800 patients from a breast cancer clinical trial and investigate the subclonal nature of the disease, and identify DNA mutations associated with resistance and poor survival.

Published
2021
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12. Genomic profile of advanced breast cancer in circulating tumour DNA

Author

Kingston, Belinda, Cutts, Rosalind J., Bye, Hannah, Beaney, Matthew, Walsh-Crestani, Giselle, Hrebien, Sarah, Swift, Claire, Kilburn, Lucy S., Kernaghan, Sarah, Moretti, Laura, Wilkinson, Katie, Wardley, Andrew M., Macpherson, Iain R., Baird, Richard D., Roylance, Rebecca, Reis-Filho, Jorge S., Hubank, Michael, Faull, Iris, Banks, Kimberly C., Lanman, Richard B., Garcia-Murillas, Isaac, Bliss, Judith M., Ring, Alistair, and Turner, Nicholas C.

Published
2021
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13. Author Correction: Genomic profile of advanced breast cancer in circulating tumor DNA

Author

Kingston, Belinda, Cutts, Rosalind J., Bye, Hannah, Beaney, Matthew, Walsh-Crestani, Giselle, Hrebien, Sarah, Swift, Claire, Kilburn, Lucy S., Kernaghan, Sarah, Moretti, Laura, Wilkinson, Katie, Wardley, Andrew M., Macpherson, Iain R., Baird, Richard D., Roylance, Rebecca, Reis-Filho, Jorge S., Hubank, Michael, Faull, Iris, Banks, Kimberly C., Lanman, Richard B., Garcia-Murillas, Isaac, Bliss, Judith M., Ring, Alistair, and Turner, Nicholas C.

Published
2021
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14. Author Correction: Genomic profile of advanced breast cancer in circulating tumor DNA

Author

Belinda Kingston, Rosalind J. Cutts, Hannah Bye, Matthew Beaney, Giselle Walsh-Crestani, Sarah Hrebien, Claire Swift, Lucy S. Kilburn, Sarah Kernaghan, Laura Moretti, Katie Wilkinson, Andrew M. Wardley, Iain R. Macpherson, Richard D. Baird, Rebecca Roylance, Jorge S. Reis-Filho, Michael Hubank, Iris Faull, Kimberly C. Banks, Richard B. Lanman, Isaac Garcia-Murillas, Judith M. Bliss, Alistair Ring, and Nicholas C. Turner

Subjects
Science
Published
2021
Full Text
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15. Costimulation blockade in combination with IL-2 permits regulatory T cell sparing immunomodulation that inhibits autoimmunity

Author

Chun Jing Wang, Lina Petersone, Natalie M. Edner, Frank Heuts, Vitalijs Ovcinnikovs, Elisavet Ntavli, Alexandros Kogimtzis, Astrid Fabri, Yassin Elfaki, Luke P. Houghton, Ralf J. Hosse, David A. Schubert, Andreas P. Frei, Ellen M. Ross, and Lucy S. K. Walker

Subjects
Abatacept, Immunomodulation, Multidisciplinary, CD28 Antigens, General Physics and Astronomy, Interleukin-2, Autoimmunity, CTLA-4 Antigen, General Chemistry, Lymphocyte Activation, T-Lymphocytes, Regulatory, General Biochemistry, Genetics and Molecular Biology
Abstract

Blockade of CD28 costimulation with CTLA-4-Ig/Abatacept is used to dampen effector T cell responses in autoimmune and transplantation settings. However, a significant drawback of this approach is impaired regulatory T cell homeostasis that requires CD28 signaling. Therefore, strategies that restrict the effects of costimulation blockade to effector T cells would be advantageous. Here we probe the relative roles of CD28 and IL-2 in maintaining Treg. We find provision of IL-2 counteracts the regulatory T cell loss induced by costimulation blockade while minimally affecting the conventional T cell compartment. These data suggest that combining costimulation blockade with IL-2 treatment may selectively impair effector T cell responses while maintaining regulatory T cells. Using a mouse model of autoimmune diabetes, we show combined therapy supports regulatory T cell homeostasis and protects from disease. These findings are recapitulated in humanised mice using clinically relevant reagents and provide an exemplar for rational use of a second immunotherapy to offset known limitations of the first.

Published
2021

16. Protease-controlled secretion and display of intercellular signals

Author

Alexander E, Vlahos, Jeewoo, Kang, Carlos A, Aldrete, Ronghui, Zhu, Lucy S, Chong, Michael B, Elowitz, and Xiaojing J, Gao

Subjects
Proto-Oncogene Proteins p21(ras), Protein Transport, HEK293 Cells, Mutation, Humans, Synthetic Biology, Flow Cytometry, Protein Engineering, Peptide Hydrolases, Signal Transduction
Abstract

To program intercellular communication for biomedicine, it is crucial to regulate the secretion and surface display of signaling proteins. If such regulations are at the protein level, there are additional advantages, including compact delivery and direct interactions with endogenous signaling pathways. Here we create a modular, generalizable design called Retained Endoplasmic Cleavable Secretion (RELEASE), with engineered proteins retained in the endoplasmic reticulum and displayed/secreted in response to specific proteases. The design allows functional regulation of multiple synthetic and natural proteins by synthetic protease circuits to realize diverse signal processing capabilities, including logic operation and threshold tuning. By linking RELEASE to additional sensing and processing circuits, we can achieve elevated protein secretion in response to "undruggable" oncogene KRAS mutants. RELEASE should enable the local, programmable delivery of intercellular cues for a broad variety of fields such as neurobiology, cancer immunotherapy and cell transplantation.

Published
2021

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