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Your search keyword '"Makris, Spyridon"' showing total 4 results
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4 results on '"Makris, Spyridon"'

1. Lymph node homeostasis and adaptation to immune challenge resolved by fibroblast network mechanics

Author

Horsnell, Harry L, Tetley, Robert J, De Belly, Henry, Makris, Spyridon, Millward, Lindsey J, Benjamin, Agnesska C, Heeringa, Lucas A, de Winde, Charlotte M, Paluch, Ewa K, Mao, Yanlan, and Acton, Sophie E

Subjects
Bioengineering, Underpinning research, 1.1 Normal biological development and functioning, Animals, Extracellular Matrix, Fibroblasts, Homeostasis, Lectins, C-Type, Lymph Nodes, Mice, Immunology
Abstract

Emergent physical properties of tissues are not readily understood by reductionist studies of their constituent cells. Here, we show molecular signals controlling cellular, physical, and structural properties and collectively determine tissue mechanics of lymph nodes, an immunologically relevant adult tissue. Lymph nodes paradoxically maintain robust tissue architecture in homeostasis yet are continually poised for extensive expansion upon immune challenge. We find that in murine models of immune challenge, cytoskeletal mechanics of a cellular meshwork of fibroblasts determine tissue tension independently of extracellular matrix scaffolds. We determine that C-type lectin-like receptor 2 (CLEC-2)-podoplanin signaling regulates the cell surface mechanics of fibroblasts, providing a mechanically sensitive pathway to regulate lymph node remodeling. Perturbation of fibroblast mechanics through genetic deletion of podoplanin attenuates T cell activation. We find that increased tissue tension through the fibroblastic stromal meshwork is required to trigger the initiation of fibroblast proliferation and restore homeostatic cellular ratios and tissue structure through lymph node expansion.

Published
2022

2. Induction of innate cytokine responses by respiratory mucosal challenge with R848 in zebrafish, mice and humans

Author

Progatzky, Fränze, Jha, Akhilesh, Wane, Madina, Thwaites, Ryan S., Makris, Spyridon, Shattock, Robin J., Johansson, Cecilia, Openshaw, Peter J., Bugeon, Laurence, Hansel, Trevor T., Dallman, Margaret J., Imperial College Healthcare Trust Biomedical Research Centre (BRC), Imperial College Healthcare NHS Trust- BRC Funding, Medical Research Council (MRC), National Institute for Health Research, Rosetrees Trust, Jha, Akhilesh [0000-0002-8413-7738], and Apollo - University of Cambridge Repository

Subjects
Adult, Gills, Male, Allergy, Immunology, mucosal innate immunity, vaccine adjuvants, Respiratory Mucosa, nasal respiratory mucosa, Article, INFLAMMATION, comparative cross-species analysis, resiquimod, INFECTION, Animals, Humans, NASAL, Immunity, Mucosal, Zebrafish, IN-VIVO, Science & Technology, Toll-Like Receptors, Imidazoles, Middle Aged, Immunity, Innate, Mice, Inbred C57BL, 1107 Immunology, CELLS, Cytokines, ASTHMA, Female, Life Sciences & Biomedicine
Abstract

We compared live zebrafish, mouse and human nasal challenge responses to the TLR7/8 agonist resiquimod (R848). We found remarkably similar induction of mediators in the three species, offering novel mucosal models of innate anti-viral immunity.

Published
2019

3. Regulatory T Cells Prevent Th2 Immune Responses and Pulmonary Eosinophilia during Respiratory Syncytial Virus Infection in Mice

Author

Durant, Lydia R., Makris, Spyridon, Voorburg, Cornelia Maaike, Loebbermann, Jens, Johansson, Cecilia, and Openshaw, Peter J. M.

Subjects
CD4-Positive T-Lymphocytes, Interleukin-13, Forkhead Transcription Factors, Mice, Transgenic, Respiratory Syncytial Virus Infections, respiratory system, CD8-Positive T-Lymphocytes, T-Lymphocytes, Regulatory, Mice, Inbred C57BL, Disease Models, Animal, Mice, Th2 Cells, Gene Knockdown Techniques, Pathogenesis and Immunity, Animals, Pulmonary Eosinophilia
Abstract

During viral infection, inflammation and recovery are tightly controlled by competing proinflammatory and regulatory immune pathways. Respiratory syncytial virus (RSV) is the leading global cause of infantile bronchiolitis, which is associated with recurrent wheeze and asthma diagnosis in later life. Th2-driven disease has been well described under some conditions for RSV-infected mice. In the present studies, we used the Foxp3(DTR) mice (which allow specific conditional depletion of Foxp3(+) T cells) to investigate the functional effects of regulatory T cells (Tregs) during A2-strain RSV infection. Infected Treg-depleted mice lost significantly more weight than wild-type mice, indicating enhanced disease. This enhancement was characterized by increased cellularity in the bronchoalveolar lavage (BAL) fluid and notable lung eosinophilia not seen in control mice. This was accompanied by abundant CD4(+) and CD8(+) T cells exhibiting an activated phenotype and induction of interleukin 13 (IL-13)- and GATA3-expressing Th2-type CD4(+) T cells that remained present in the airways even 14 days after infection. Therefore, Treg cells perform vital anti-inflammatory functions during RSV infection, suppressing pathogenic T cell responses and inhibiting lung eosinophilia. These findings provide additional evidence that dysregulation of normal immune responses to viral infection may contribute to severe RSV disease.

Published
2013

4. Induction of innate cytokine responses by respiratory mucosal challenge with R848 in zebrafish, mice, and humans

Author

Progatzky, Fränze, Jha, Akhilesh, Wane, Madina, Thwaites, Ryan S, Makris, Spyridon, Shattock, Robin J, Johansson, Cecilia, Openshaw, Peter J, Bugeon, Laurence, Hansel, Trevor T, and Dallman, Margaret J

Subjects
Adult, Gills, Male, Toll-Like Receptors, Imidazoles, Respiratory Mucosa, Middle Aged, Immunity, Innate, 3. Good health, Mice, Inbred C57BL, Animals, Cytokines, Humans, Female, Immunity, Mucosal, Zebrafish

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