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- 2019
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Tidskriftsartikel (refereegranskat)
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- Alisjahbana, A, et al.
(författare)
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CD5 Surface Expression Marks Intravascular Human Innate Lymphoid Cells That Have a Distinct Ontogeny and Migrate to the Lung
- 2021
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 12, s. 752104-
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Tidskriftsartikel (refereegranskat)abstract
- Innate lymphoid cells (ILCs) contribute to immune defense, yet it is poorly understood how ILCs develop and are strategically positioned in the lung. This applies especially to human ILCs due to the difficulty of studying them in vivo. Here we investigated the ontogeny and migration of human ILCs in vivo with a humanized mouse model (“MISTRG”) expressing human cytokines. In addition to known tissue-resident ILC subsets, we discovered CD5-expressing ILCs that predominantly resided within the lung vasculature and in the circulation. CD5+ ILCs contained IFNγ-producing mature ILC1s as well as immature ILCs that produced ILC effector cytokines under polarizing conditions in vitro. CD5+ ILCs had a distinct ontogeny compared to conventional CD5- ILCs because they first appeared in the thymus, spleen and liver rather than in the bone marrow after transplantation of MISTRG mice with human CD34+ hematopoietic stem and progenitor cells. Due to their strategic location, human CD5+ ILCs could serve as blood-borne sentinels, ready to be recruited into the lung to respond to environmental challenges. This work emphasizes the uniqueness of human CD5+ ILCs in terms of their anatomical localization and developmental origin compared to well-studied CD5- ILCs.
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- Brownlie, D, et al.
(författare)
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Comparison of Lung-Homing Receptor Expression and Activation Profiles on NK Cell and T Cell Subsets in COVID-19 and Influenza
- 2022
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 13, s. 834862-
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Tidskriftsartikel (refereegranskat)abstract
- Respiratory viral infections with SARS-CoV-2 and influenza viruses commonly induce a strong infiltration of immune cells into the human lung, with potential detrimental effects on the integrity of the lung tissue. Despite comprising the largest fractions of circulating lymphocytes in the lung, rather little is known about how peripheral blood natural killer (NK) cell and T cell subsets are equipped for lung-homing in COVID-19 and influenza. Here, we provide a detailed comparative analysis of NK cells and T cells in patients infected with SARS-CoV-2 or influenza virus, focusing on the protein and gene expression of chemokine receptors known to be involved in recruitment to the lung. For this, we used 28-colour flow cytometry as well as re-analysis of a publicly available single-cell RNA-seq dataset from bronchoalveolar lavage (BAL) fluid. Frequencies of NK cells and T cells expressing CXCR3, CXCR6, and CCR5 were altered in peripheral blood of COVID-19 and influenza patients, in line with increased transcript expression of CXCR3, CXCR6, and CCR5 and their respective ligands in BAL fluid. NK cells and T cells expressing lung-homing receptors displayed stronger phenotypic signs of activation compared to cells lacking lung-homing receptors, and activation was overall stronger in influenza compared to COVID-19. Together, our results indicate a role for CXCR3+, CXCR6+, and/or CCR5+ NK cells and T cells that potentially migrate to the lungs in moderate COVID-19 and influenza patients, identifying common targets for future therapeutic interventions in respiratory viral infections.
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- Harris, Anna E., et al.
(författare)
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Exploring anti-androgen therapies in hormone dependent prostate cancer and new therapeutic routes for castration resistant prostate cancer
- 2022
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media S.A.. - 1664-2392. ; 13
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Forskningsöversikt (refereegranskat)abstract
- Androgen deprivation therapies (ADTs) are important treatments which inhibit androgen-induced prostate cancer (PCa) progression by either preventing androgen biosynthesis (e.g. abiraterone) or by antagonizing androgen receptor (AR) function (e.g. bicalutamide, enzalutamide, darolutamide). A major limitation of current ADTs is they often remain effective for limited durations after which patients commonly progress to a lethal and incurable form of PCa, called castration-resistant prostate cancer (CRPC) where the AR continues to orchestrate pro-oncogenic signalling. Indeed, the increasing numbers of ADT-related treatment-emergent neuroendocrine-like prostate cancers (NePC), which lack AR and are thus insensitive to ADT, represents a major therapeutic challenge. There is therefore an urgent need to better understand the mechanisms of AR action in hormone dependent disease and the progression to CRPC, to enable the development of new approaches to prevent, reverse or delay ADT-resistance. Interestingly the AR regulates distinct transcriptional networks in hormone dependent and CRPC, and this appears to be related to the aberrant function of key AR-epigenetic coregulator enzymes including the lysine demethylase 1 (LSD1/KDM1A). In this review we summarize the current best status of anti-androgen clinical trials, the potential for novel combination therapies and we explore recent advances in the development of novel epigenetic targeted therapies that may be relevant to prevent or reverse disease progression in patients with advanced CRPC.
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- Sinn, T., et al.
(författare)
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Lessons learned from three university experiments onboard the REXUS/BEXUS sounding rockets and stratospheric balloons
- 2013
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Ingår i: 64th International Astronautical Congress 2013. - : International Astronautical Federation. - 9781629939094 ; , s. 7965-7976
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Konferensbidrag (refereegranskat)abstract
- Over the last three years the authors have been involved in three experiments that were or will be launched on sounding rockets and high altitude balloons with the REXUS/BEXUS program (Rocket-borne / Balloon-borne Experiments for University Students). The first experiment, called Suaineadh was launched from Esrange (Kiruna, Sweden) onboard REXUS 12 in March 2012. Suaineadh had the purpose of deploying a web in space by using centrifugal forces. The payload was lost during re-entry but was recovered 18 month later in early September 2013. StrathSat-R is the second experiment, which had the purpose of deploying two cube satellites with inflatable structures from the REXUS 13 sounding rocket, was launched first in May 2013 and will be launched a second time in spring 2014. The last experiment is the iSEDE experiment which has the goal of deploying an inflatable structure with disaggregated electronics from the high altitude balloon BEXUS15/16 in October 2013. All these experiments have been designed, built and flown in a timeframe of one and a half to two years. This paper will present the lessons learned in project management, outreach, experiment design, fabrication and manufacturing, software design and implementation, testing and validation as well as launch, flight and post-flight. Furthermore, the lessons learned during the recovery mission of Suaineadh will be discussed as well. All these experiments were designed, built and tested by a large group of university students of various disciplines and different nationalities. StrathSat-R and iSEDE were built completely at Strathclyde but the Suaineadh experiment was a joint project between Glasgow and Stockholm which was especially tricky during integration while approaching the experiment delivery deadline. This paper should help students and professionals across various disciplines to build and organise these kinds of projects more efficiently without making the same, sometimes expensive, mistakes all over again.
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