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Identifier 000460055
Title Analysis of group 2 innate lymphoid cells in murine models of experimental arthritis
Alternative Title Ανάλυση των τύπου 2 λεμφοκυττάρων της έμφυτης ανοσίας σε πειραματικά μοντέλα αρθρίτιδας
Author Χανής, Θεόδωρος
Thesis advisor Σιδηρόπουλος, Πρόδρομος
Reviewer Μπερτσιάς, Γεώργιος
Βεργίνης, Παναγιώτης
Abstract Innate Lymphoid Cells, or ILCs, are a heterogeneous innate immune cell population typically characterized as the innate counterpart of T cells. Deregulation of ILC subsets has already been described in patients with Rheumatoid Arthritis (RA). Published data have showcased that Group 2 Innate Lymphoid Cells (ILC2s) are higher in the periphery of RA patients and have been negatively correlated with disease activity. In parallel, it has been shown that murine ILC2s can facilitate the resolution of arthritis by activating type 2 immune responses and inhibiting synovial macrophages and primed osteoclasts, rescuing the bone tissue from erosion. On the other hand, recent data revealed that Th17-mediated activation of ILC2s exacerbated arthritis through GM-CSF production by ILC2s, resulting in the activation of macrophages and stromal cells. Our hypothesis is that ILC2s may have pleiotropic roles within the context of inflammatory arthritis, acquiring either an immunoregulatory or a destructive phenotype depending on environmental cues. Thus, the aim of the project was to investigate the plasticity of ILC2s, uncover their distribution among murine tissues and delineate their role in synovial inflammation, utilizing murine models of experimental arthritis. We therefore identified ILC2s in tissues associated with experimental arthritis inflammation, such as the draining lymph nodes, the spleen and the synovial tissue of arthritic mice, as well as in the periphery and in distal organs like the lungs. Additionally, we monitored the kinetics of the ILC2 population in the periphery from disease onset to disease establishment and observed differential enrichment of. Finally, we isolated ILC2s from arthritic and assessed the expression levels of hallmark genes and transcription factors indicative of their functionality in the context of disease. Our data reveal a differential distribution of ILC2 subsets among tissues, with natural ILC2s (nILC2s) being mostly increased in the draining lymph nodes and synovial tissue of arthritic mice and inflammatory ILC2s (iILC2s) being increased in the periphery and the lungs of arthritic mice with established arthritis. The increased numbers of iILC2s in the lung may indicate a distal activation of ILC2s and the presence of a potent migratory population that can travel towards the synovial tissue. Lastly, K/BxN ILC2s exhibited an ex-ILC2 phenotype close to Group 3 Innate Lymphoid Cells (ILC3s), with increased expression of IL-17 which may be associated with specific disease features.
Language English
Subject Rheumatoid arthritis
Ρευματοειδής αρθρίτιδα
Issue date 2023-12-08
Collection   School/Department--School of Medicine--Department of Medicine--Post-graduate theses
  Type of Work--Post-graduate theses
Permanent Link https://elocus.lib.uoc.gr//dlib/e/a/d/metadata-dlib-1699348165-986153-21756.tkl Bookmark and Share
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