Evidence of a role for B cell–activating factor of the TNF family in the pathogenesis of chronic rhinosinusitis with nasal polyps (original) (raw)
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Evaluation of the presence of B-cell attractant chemokines in chronic rhinosinusitis
American Journal of Rhinology and Allergy, 2010
Background-B-cell responses may play a role in the pathogenesis of nasal polyposis via local IgA and IgE production and activation of eosinophils and mast cells. B-cell attracting chemokines may therefore have relevance in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNPs)
Molecular Medicine Reports
The present study focused on the assessment of the inflammatory infiltrate that characterizes nasal polyps in patients with chronic rhinosinusitis and nasal polyposis. Inflammatory cell type was determined using specific markers. This evaluation was made possible by determining the expression of the following markers: CD20, a marker of B lymphocytes [using activated T cells (ATC) armed with CD20 antibody]; CD3, a marker of T lymphocytes (using ATC armed with anti-CD3 antibody); CD45, the leukocyte common antigen (using ATC armed with anti-CD45 antibody; and CD34, for the microvasculature of the nasal polyp (using anti-CD34 antibody). The diagnosis of chronic rhinosinusitis with nasal polyps (CRSwNP) was made according to current EPOS guidelines based on patient history, clinical examination and nasal endoscopy. We examined surgically resected nasal polyps from 127 patients diagnosed with CRSwNP, who benefited from surgical procedures at the Department of Otorhinolaryngology of our institution. The polyps were analyzed at the Department of Pathology of our institution utilizing histopathological and immunohistochemical methods as follows: Firstly, the tissues were paraffin-impregnated, sectioned and stained with hematoxylin and eosin. We then examined the expression of CD3, CD20, CD34 and CD45RO by immunohistochemistry with soluble labeled streptavidin biotin (LSAB)/horseradish peroxidase (HRP) complexes. We observed the following histopathological changes: The structure of the epithelium was evidenced by collagenous subjacent stroma with mixed areas, sometimes associated with hyaline zones. In all types of polyps, we also observed a diffuse underlayer or periglandular lymphoplasmacytic in filtrate composed predominantly from T lymphocytes and eosinophils. The histopathological changes suggest the chronic inflammation of the sinus mucosa, which was diffusely distributed in allergic polyps and with nodular distribution in fibro-inflammatory polyps. The number of B lymphocytes was greater in the fibro-inflammatory polyps. On the whole, the findings of this study indicate that the inflammatory infiltrate in nasal polyps from patients with CRSwNP is mainly composed of T cells and eosinophils in all types of polyposis. In addition, a diffuse distribution of allergic polyps and the nodular distribution of fibro-inflammatory polyps, and the hyperplasia of the seromucous glands was observed. The determination of CD20, CD3, CD34 and CD45RO could be used to assess the inflammatory infiltrate of the nasal poplyps in these patients.
Cytokine Signature and Involvement in Chronic Rhinosinusitis with Nasal Polyps
International Journal of Molecular Sciences, 2021
Cytokines are well known to play a central role in chronic rhinosinusitis with nasal polyps (CRSwNP), particularly in maintenance of the inflammatory response and the recruitment of eosinophils. The pathophysiological concepts concerning the involvement of inflammatory cytokines in CRSwNP have gradually evolved. Although the Th2 cytokines environment associated with an eosinophilic infiltration has retained a central role in the genesis of polyps, the role of other cytokine subpopulations has also and more recently been detailed, leading to a specific and complex signature in CRSwNP. The purpose of this review is to summarize the current state of knowledge about the cytokine signature in CRSwNP, the role of cytokines in the pathogenesis of this disease and in the intercellular dialog between epithelial cells, fibroblasts and inflammatory cells. Knowledge of this precise cytokine signature in CRSwNP is fundamental in the perspective of potential targeting biotherapies.
Increased expression of the chemokine CCL23 in eosinophilic chronic rhinosinusitis with nasal polyps
Journal of Allergy and Clinical Immunology, 2011
Background-Chronic rhinosinusitis (CRS) is a heterogeneous chronic disease characterized by local inflammation of the sinonasal tissues. The pathogenesis of CRS remains controversial but it has been associated with the accumulation of various immune and inflammatory cells in sinus tissue. Objectives-The objective of this study was to investigate the expression of chemokine CCL23, known to bind to CCR1 and recruit monocytes, macrophages, and dendritic cells, in patients with CRS. Methods-We collected nasal tissue from patients with CRS and control subjects. We assayed mRNA for CCL23 by using real-time PCR and measured CCL23 protein by ELISA, immunohistochemistry and immunofluorescence. Results-CCL23 mRNA was significantly elevated in nasal polyps from patients with polypoid CRS (CRSwNP) (p<0.05) compared to inferior turbinate and uncinate tissue from patients with CRS or control subjects. CCL23 protein was also elevated in nasal polyps, although these levels were not statistically significant. Immunohistochemical analysis revealed CCL23 expression in mucosal epithelial cells and inflammatory cells, but accumulation of CCL23 positive inflammatory cells occurred only in nasal polyps. Immunofluorescence data showed CCL23 colocalization with ECP positive eosinophils. The concentration of CCL23 in nasal polyps positively correlated with the concentration of ECP, suggesting that eosinophils are major CCL23 producing
Involvement of inflammatory cells in chronic rhinosinusitis with nasal polyps
Romanian Journal of Morphology and Embryology, 2020
Inflammation plays an important role in the pathogenesis of nasal polyps. Understanding the biomolecular action mechanisms of inflammatory elements can contribute to improving the prognosis of these lesions. The study analyzed the distribution and immunohistochemically quantified eosinophils [eosinophil major basic protein (BMK-13)], lymphocytes [cluster of differentiation (CD) 4, CD8, CD20] and plasmocytes (CD138) in both the epithelial and stromal compartment in relation to composite scores, which included specific histopathological parameters for 50 sinonasal polyps. Inflammatory elements predominated at stromal level, the high histological composite scores being frequently associated with increased expression of inflammatory elements. Also, the numerical distribution of inflammatory elements indicated positive linear relations within the groups BMK-13/CD8 and CD4/CD20/CD138, and a negative linear relation between the two groups. This aspect can support the existence of alternati...
Allergy, Asthma & Clinical Immunology
Background Chronic rhinosinusitis (CRS) describes an inflammatory condition affecting the sinonasal mucosa. As the immune system players such as immunoglobulins play prominent roles in the development of CRS, we aimed to investigate the expression of IgA subclasses and factors involved in IgA class switching in the sinonasal mucosa of CRS patients. Methods Specimens were collected from the sinonasal mucosa of the healthy controls and CRS patients. Histological assessments were performed by H&E and immunohistochemistry. Real-time PCR and ELISA methods were applied to measure gene expression and protein levels extracted from tissue samples, respectively. Results We observed that total IgA and subclass-positive cells were higher in the patient groups than controls. There was a significant correlation between the number of eosinophils and total IgA and subclasses-positive cells (Pv
Clinical <html_ent glyph="@amp;" ascii="&"/> Experimental Allergy, 1998
Background Eosinophils are a prominent feature of chronic hyperplastic sinusitis with nasal polyposis (CHS/NP). Our previous studies showed that their presence was associated with the expression of GM-CSF and RANTES mRNA. In allergic NP, increased expression of IL-5 was also found. Objective We wished to examine cytokine immunoreactivity for IL-5, GM-CSF and RANTES mRNA in allergic and non-allergic NP and compare immunoreactivity with expression of cytokine mRNA by in situ hybridization. Methods NP were obtained from five allergic and eight non-allergic subjects with CHS/ NP. Middle turbinate tissue from eight normal subjects were used as controls. Cellassociated cytokine mRNA was detected by in situ hybridization (ISH). Cytokine immunoreactive cells were enumerated by immunostaining. Colocalization immunostaining was also performed to identify specific cell types producing IL-5. Results Immunostaining for GM-CSF, IL-5 and RANTES protein was increased in both allergic and non-allergic NP compared with control middle turbinates. Allergic polyps contained greater numbers of IL-5 immunoreactive cells (P ¼ 0.01), whereas non-allergic polyps contained greater numbers of GM-CSF immunoreactive cells (P ¼ 0.04). Immunostaining was primarily associated with inflammatory cells, but immunostaining for RANTES and, to a lesser extent GM-CSF, was also seen in the epithelium. The density of immunoreactive cells was variably correlated with cytokine mRNA þ cells (GM-CSF: R ¼ 0.56, P ¼ 0.05; IL-5: R ¼ 0.76, P ¼ 0.003; and RANTES: R ¼ 0.89, P ¼ 0.0005). Colocalization immunostaining revealed that the majority of IL-5 immunoreactive cells in both allergic and non-allergic NP were T lymphocytes. However, allergic NP contained greater numbers of IL-5 þ /CD3 þ T lymphocytes and IL-5 þ mast cells, whereas non-allergic NP contained greater numbers of IL-5 þ eosinophils. Conclusion We conclude that GM-CSF, IL-5 and RANTES are produced in increased amounts in both allergic and non-allergic NP. Distinguishing features of non-allergic NP include fewer numbers of CD3 T lymphocytes, fewer IL-5 þ /CD3 þ T lymphocytes and greater numbers of IL-5 þ eosinophils. These differences may suggest different mechanisms of eosinophil accumulation and activation in allergic vs non-allergic NP.
T-cell phenotypes in chronic rhinosinusitis with nasal polyps in Japanese patients
Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology, 2015
Chronic rhinosinusitis with nasal polyps is characterized by local inflammation and is categorized into two subtypes in Japan: eosinophilic chronic rhinosinusitis, and non-eosinophilic chronic rhinosinusitis. The objective of this study was to investigate the expression of key transcription factors for Treg and Th1/Th2/Th17 cells, in relation to the mRNA expression of representative cytokines in these two subtypes of chronic rhinosinusitis with nasal polyps. The expression of forkhead box P3 (FOXP3), T-box transcription factor (T-bet), GATA3, retinoid acid-related orphan receptor C (RORc), the suppressive cytokines TGF-β1 and IL-10, and Th1/Th2/Th17 cytokines (IFN-γ, IL-4, IL-5, IL-13, IL-17) were analyzed by means of RT-PCR in eosinophilic polyps. Eosinophilic polyps were defined as having an eosinophil count of more than 50 per microscopic field (×400 magnification) using five fields located in the subepithelial area of the polyps, while the non-eosinophilic polyps and controls di...