Lung lymphoid neogenesis in cystic fibrosis: a model of adaptive responses to bacteria?

Gohy, Sophie; Ladjemi, Maha Zohra; Pilette, Charles

doi:10.1183/13993003.00380-2017

Cited by 3 publications

(3 citation statements)

References 26 publications

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“…When the B cell-depleting anti-CD20 antibody rituximab was administered to two CF patients prior to receiving lung transplants, lymphoid aggregates were not disrupted and their role in CF lung pathogenesis could not be determined [113]. Although lymphoid follicle formation can be induced by bacterial lung infection [112] and their presence has been identified in end stage CF [54], further investigation into the role of lymphoid neogenesis in CF is needed to determine if they should be targeted therapeutically [114]. Possible therapeutics to disrupt lymphocyte aggregation in the airways could target the chemokines responsible for B cell recruitment.…”

Section: B Cellsmentioning

confidence: 99%

Immunomodulation in Cystic Fibrosis: Why and How?

Giacalone

Dobosh

Gaggar

et al. 2020

IJMS

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Cystic fibrosis (CF) lung disease is characterized by unconventional mechanisms of inflammation, implicating a chronic immune response dominated by innate immune cells. Historically, therapeutic development has focused on the mutated cystic fibrosis transmembrane conductance regulator (CFTR), leading to the discovery of small molecules aiming at modulating and potentiating the presence and activity of CFTR at the plasma membrane. However, treatment burden sustained by CF patients, side effects of current medications, and recent advances in other therapeutic areas have highlighted the need to develop novel disease targeting of the inflammatory component driving CF lung damage. Furthermore, current issues with standard treatment emphasize the need for directed lung therapies that could minimize systemic side effects. Here, we summarize current treatment used to target immune cells in the lungs, and highlight potential benefits and caveats of novel therapeutic strategies.

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Section: B Cellsmentioning

confidence: 99%

Immunomodulation in Cystic Fibrosis: Why and How?

Giacalone

Dobosh

Gaggar

et al. 2020

IJMS

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“…In lung tissue, TLOs are considered as a hallmark of autoimmune disease such as rheumatoid arthritis and Sjögren syndrome but can also be found in chronic infection and various other lung pathologies [53][54][55]. The exact role of iBALT is a field of active research and their exact composition may be pivotal in defining their function [56,57]. Our approach plays an important role in translational research to better define, characterize, and by this understand the patterns of chronic inflammation in the lung.…”

Section: Application To Biomedical Contextmentioning

confidence: 99%

Graph-based description of tertiary lymphoid organs at single-cell level

Schaadt

Schönmeyer²,

Forestier

et al. 2020

PLoS Comput Biol

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Our aim is to complement observer-dependent approaches of immune cell evaluation in microscopy images with reproducible measures for spatial composition of lymphocytic infiltrates. Analyzing such patterns of inflammation is becoming increasingly important for therapeutic decisions, for example in transplantation medicine or cancer immunology. We developed a graph-based assessment of lymphocyte clustering in full whole slide images. Based on cell coordinates detected in the full image, a Delaunay triangulation and distance criteria are used to build neighborhood graphs. The composition of nodes and edges are used for classification, e.g. using a support vector machine. We describe the variability of these infiltrates on CD3/CD20 duplex staining in renal biopsies of long-term functioning allografts, in breast cancer cases, and in lung tissue of cystic fibrosis patients. The assessment includes automated cell detection, identification of regions of interest, and classification of lymphocytic clusters according to their degree of organization. We propose a neighborhood feature which considers the occurrence of edges with a certain type in the graph to distinguish between phenotypically different immune infiltrates. Our work addresses a medical need and provides a scalable framework that can be easily adjusted to the requirements of different research questions. Author summaryIn this study, we developed a workflow to detect and classify immune infiltrates in gigapixel microscopy images. It allowed us to measure the degree of organization in lymphocyte clusters with graph-based features and finally to distinguish between tertiary lymphoid organs and other infiltrates. As a clinically relevant use case, we applied it to three different types of tissues and diseases. Our method addresses the need for observer-independent, large-scale evaluation of immune cell patterns and is a prerequisite to capture PLOS Computational Biology | https://doi.

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“…A central question regarding lymphoid neogenesis in COPD lungs relates to the antigenic trigger of this process. There are several possibilities, ranging from adaptive immunity to microbial antigens, as observed in cystic fibrosis (4, 5), to autoreactivity to (modified) self-antigens, as described in emphysema (6, 7). A longitudinal study could indeed be informative about the clinical and pathological events that precede the development of LFs in the COPD lung; however, such a study would be challenging given the need for repeated sampling of the distal lung.…”

mentioning

confidence: 99%