Abstract
Activated TH2 cells and eosinophils are hallmarks of the allergic inflammation seen in patients with allergic rhinitis (AR). However, which cells activate and attract Tcells and eosinophils to the inflammatory lesion has not been determined. We wanted to assess the role of mucosal mononuclear phagocytes, consisting of monocytes, macrophages, and dendritic cells, in the local allergic inflammatory reaction. Patients with AR and nonatopic control subjects were challenged with pollen extract, and nasal symptoms were recorded. Mucosal biopsy specimens obtained at different time points before and after challenge were used for immunostaining in situ and flow cytometric cell sorting. Sorted mononuclear phagocytes were subjected to RNA extraction and gene expression profiling. In an invivo model of AR, we found that CD14(+) monocytes were recruited to the nasal mucosa within hours after local allergen challenge, whereas conventional dendritic cells accumulated after several days of continued provocation. Transcriptomic profiling of mucosal mononuclear phagocytes sorted after 1week of continued allergen challenge showed an activated phenotype at least partially driven by IL-4 signaling, IL-13 signaling, or both. Importantly, gene expression of several TH2-related chemokines was significantly upregulated by the mononuclear phagocyte population concomitant with an increased recruitment of CD4(+) Tcells and eosinophils. Our findings suggest that the mononuclear phagocyte population is directly involved in the production of proinflammatory chemokines that attract other immune cells. Rapid recruitment of CD14(+) monocytes to the challenged site indicates that these proinflammatory mononuclear phagocytes have a central role in orchestrating local allergic inflammation.
Highlights
Results in paper III suggest that a stable chimerism is achieved between donor-derived alveolar macrophages (AMs) that survive the transplantation and AMs derived from monocytes recruited after the surgery
In lung cancer patients the density of AMs in areas distal from the tumor was similar to that resulting from the addition of donor- and recipient-derived AMs in lung transplanted patients one year after the surgery
Mouse models of lung inflammation have shown that during respiratory infections most resident macrophages die and high numbers of monocytes are recruited to the lung [269]
Summary
Allergic rhinitis (AR) and allergic asthma are chronic inflammatory disorders of the respiratory mucosa caused by sensitization to environmental allergens. Asthma was largely regarded as a psychosomatic illness during the first half of 20th century, until the 1960s when anti-inflammatory medications started to be successfully administered to asthma patients. In the second half of the 20th century the number of primary-care consultations due to AR dramatically increased in the Western World [8]. This trend was followed by other allergic diseases like asthma and atopic eczema [9]. Nowadays respiratory allergy is a global health care problem, and AR alone affects more than 400 million people worldwide, especially in the western societies [10], but the incidence in developing countries increases as they acquire a westernized lifestyle. Page |8 knowledge about their precursors and longevity might pave the way to novel therapeutic strategies for patients with immune-mediated respiratory diseases
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