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The role of DC subsets in respiratory viral infections and vaccination : a case of mistaken identity
No full textImmune activation at the lung epithelial barrier
Get PDFDendritic cells (DCs) are commonly known as the most potent antigen presenting cells in several inflammatory diseases. In the lung the main function of DCs is to sample incoming antigens, transport them to the draining lymph nodes, where they will activate naïve T cells to become effector T cells or regulatory T cells. The outcome of the response depends on the type of antigen, the type of instructing signals encountered in the periphery but also on the nature of the dendritic cell subsets presenting the antigen to T cells.
In chapter 3 we have tried to understand the immune response developed towards antigens trapped in the lung vascular filter. We have shown that these antigens were presented to T cells by interstitial lung DCs in the mediastinal lymph nodes. In addition, we found that these interstitial lung DCs secrete monocyte-chemotactic protein-1 (MCP-1) after embolic antigen exposure, leading to the recruitment of monocytes. Deletion of interstitial DCs resulted in reduced inflammatory aggregates in the lung and antigen presentation in the MLN. Adoptive transfer of purified bone marrow monocytes into DC- depleted mice resulted in conversion of injected monocytes into monocyte-derived DCs and presentation of the antigen in the MLN.
In chapter 4 we describe that bile acid ursodeoxycholic acid (UDCA) has immune regulatory properties by directly acting on the nuclear farnesoid X receptor on DCs. Treatment with UDCA during the secondary immune responses resulted in reduced features of allergic airway inflammation. Recent studies revealed an important role for structural cells, especially epithelial cells, in allergic asthma. Lung epithelial cells express pattern recognition receptors (such as TLR4) and respond to allergens by producing DC-instructing factors. Chapter 5 demonstrates that exposure of lung epithelial cells to HDM leads to release of uric acid (UA). Secreted UA acts as a danger signal to promote Th2 immune responses to harmless inhaled antigens. UA-driven responses were mediated by DCs through Syk and PI3Kd signalling pathway. Treatment of mice with uricase at the time of HDM sensitization reduced the features of allergic airway inflammation.
Chapter 6 shows that after HDM exposure, IL-1a is one of the key cytokines released by epithelial cells and acts in an autocrine loop to enhance Th2 inflammatory responses. Signalling through the IL-1a/IL-1RI pathway induces the secretion of various chemokines and Th2 instructing cytokines by lung epithelial cells. We found that IL-1a induced production of IL-33 and GM-CSF by lung epithelial cells. These two cytokines were found to be crucial in driving Th2 immunity to HDM. Unexpectedly, we also found that epithelial-derived thymic-stromal lymphopoietin (TSLP) did not play a role in a mild model of HDM-induced asthma. However, the use of higher doses of HDM (inducing more severe asthma features) revealed a more important role for TSLP.
In conclusion, this thesis shows that lung DCs are important for the sampling of antigens in different lung compartments. In some cases, like upon exposure to inhaled allergen such as HDM, epithelial cell-derived factors control DC-induced responses. This crosstalk between epithelial cells and DCs involves cytokines such as IL-1a, IL-33 and GM-CSF but also endogenous danger signals like uric acid. Our findings place airway epithelial cells at the origin of Th2 sensitization and therefore, airway epithelial cells can be considered as a therapeutic target for allergic asthma
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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