IgE and mast cells in allergic disease
Immunoglobulin E (IgE) antibodies and mast cells have been so convincingly linked to the pathophysiology of anaphylaxis and other acute allergic reactions that it can be difficult to think of them in other contexts. However, a large body of evidence now suggests that both IgE and mast cells are also key drivers of the long-term pathophysiological changes and tissue remodeling associated with chronic allergic inflammation in asthma and other settings. Such potential roles include IgE-dependent regulation of mast-cell functions, actions of IgE that are largely independent of mast cells and roles of mast cells that do not directly involve IgE. In this review, we discuss findings supporting the conclusion that IgE and mast cells can have both interdependent and independent roles in the complex immune responses that manifest clinically as asthma and other allergic disorders.
[Show abstract] [Hide abstract] ABSTRACT: Basophils have become increasingly recognized as important innate immune cells that mediate antihelminth immunity and barrier inflammation. Recent discoveries have uncovered previously unrecognized heterogeneity in basophil populations. However, how diversity in basophil regulation and function impacts human disease remains poorly defined. The goal of the present review is to highlight how new insights into basophil heterogeneity can help us to better understand disease pathogenesis and inform the development of new therapeutics.
- "The best studied mechanism of basophil activation is crosslinking of IgE with its high-affinity receptor FcεRI . In response to IgE-mediated activation, basophils degranulate to rapidly release a variety of effector molecules such as histamine and adenosine triphosphate (ATP) [3, 62]. "
[Show abstract] [Hide abstract] ABSTRACT: Connexins are transmembrane proteins that can generate intercellular communication channels known as gap junctions. They contribute to the direct movement of ions and larger cytoplasmic solutes between various cell types. In the lung, connexins participate in a variety of physiological functions, such as tissue homeostasis and host defence. In addition, emerging evidence supports a role for connexins in various pulmonary inflammatory diseases, such as asthma, pulmonary hypertension, acute lung injury, lung fibrosis or cystic fibrosis. In these diseases, the altered expression of connexins leads to disruption of normal intercellular communication pathways, thus contributing to various pathophysiological aspects, such as inflammation or tissue altered reactivity and remodelling. The present review describes connexin structure and organization in gap junctions. It focuses on connexins in the lung, including pulmonary bronchial and arterial beds, by looking at their expression, regulation and physiological functions. This work also addresses the issue of connexin expression alteration in various pulmonary inflammatory diseases and describes how targeting connexin-based gap junctions with pharmacological tools, synthetic blocking peptides or genetic approaches, may open new therapeutic perspectives in the treatment of these diseases.
- "Finally, although a precise role of Cx43 in inflammation associated with lung allergic diseases has not been investigated yet, Cx43 protein is expressed on the cytoplasmic membrane of murine bone marrow cultured mast cells and of a murine mast cell line, suggesting that mast cells have the potential to communicate with other cells in their microenvironment through GJs (Vliagoftis et al., 1999). As mast cells are key drivers of pathophysiological changes and tissue remodeling, associated with chronic allergic inflammation in asthma and other allergic disorders (Galli & Tsai, 2012), their communication with adjacent cells such as fibroblasts or smooth muscle cells through GJs may therefore play a role in the development and persistence of lung inflammation. Moreover , human peripheral blood eosinophils from atopic individuals also express Cx43 constitutively, with formation of functional GJs allowing communication of eosinophils with epithelial or endothelial cells (Vliagoftis et al., 2014). "
[Show abstract] [Hide abstract] ABSTRACT: Pollen grains are well established to be an important cause of respiratory allergy. Current pharmacologic therapies for allergic asthma do not cure the disease. Allergen specific immunotherapy is the only treatment method which re-directs the immune system away from allergic response leading to a long lasting effect. The mechanism by which immunotherapy achieves this goal is an area of active research world-wide. The present experimental study was designed to develop an experimental model of allergic lung inflammation based on a relevant human allergen, Alstonia scholaris pollen, and to establish the immunological and cellular features of specific allergen immunotherapy using this same pollen extract. Our results revealed that Alstonia scholaris pollen sensitization and challenge causes eosinophilic airway inflammation with mucin hypersecretion. This is associated with increased total IgE, increased expression of FcεRI on lung mast cells and increased levels of IL-4, IL-5 & IL-13 as confirmed by ELISA, in-situ immunofluorescence and FACS assay. Allergen specific immunotherapy reduced airway inflammation and also decreased total IgE level, FcεRI expression, IL-4, IL-5 & IL-13 levels. It was further noted that the reduction of these levels was more by intra-nasal route than by intra-peritoneal route. Thus we present a novel animal model of Alstonia scholaris pollen allergic disease and specific allergen immunotherapy which will pave the way towards the development of better treatment modalities.
- "13 in a rat model of airway allergy achieved by immunotherapy Interleukin 13 (IL 13) induces goblet cell hyperplasia and mucus hy- persecretion [58,59] and immunotherapy reduces IL 13 level . In lymphocyte there was significant upregulation (p b 0.001) of IL 13 in Alstonia group (Fig. 7 ) (F (4,25) = 489.82) "