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Objectives/Hypothesis Hypoxia-inducible factor-1α (HIF-1α) is considered as a key molecule in regulating Th17:regulatory T-cells (Tregs) balance. The aims of this study were to investigate whether HIF-1α is associated with the RORγ (RAR-related orphan receptor gamma) expression of Tregs in nasal polyps and to verify whether Staphylococcus enterotoxin B (SEB) is involved in this process. Study Design Clinical experimental study. Methods Forty patients with chronic rhinosinusitis with nasal polyposis were enrolled and divided into eosinophilic nasal polyps (EPs) and noneosinophilic nasal polyps (NEPs) according to the proportion of eosinophils. Fifteen subjects who were undergoing septoplasty were enrolled as control subjects. Expression of HIF-1α in the tissue was measured using reverse transcriptase-polymerase chain reaction (RT-PCR), Western blot, and flow cytometry. The mRNA expression of RORC (RAR-related orphan receptor C) and HIF-1α in Tregs separated from tissues were measured by RT-PCR. Double immunofluorescent staining for RORC/FOXP3 and HIF-1α/FOXP3 were conducted on the tissues. Expression of RORC and HIF-1α in Tregs from peripheral blood mononuclear cells (PBMCs) was measured using flow cytometry after stimulation with SEB. Results Expression of RORC and HIF-1α in Tregs was significantly higher in EPs and NEPs compared with control mucosa, and there was a significant correlation between RORC and HIF-1α expression in Tregs. Expression of RORC and HIF-1α mRNA in Tregs separated from the tissues was also significantly higher in nasal polyps compared with control mucosa. Expression of RORC and HIF-1α in Tregs were increased after 24-hour stimulation with SEB in the PBMCs. Conclusions HIF-1α-induced RORC expression in Tregs may play a key role in the pathogenesis of nasal polyps. Level of Evidence NA Laryngoscope, 124:E151-E159, 2014 [ABSTRACT FROM AUTHOR]

Background: The pathogenesis of nasal polyposis has not been fully understood. Recent studies indicate that there is a subset of CD4+CD25highFoxP3+T cells (regulatory T cells [Tregs]) that express retinoic acid receptor related orphan receptor C (RORC) or IL-17, and these cells might be new proinflammatory cells because of the expression of IL-17 with loss of their suppressive function. The goals of this study were to localize Th17-like Tregs (Th17-like Tregs or RORC+Tregs) in nasal polyps and to investigate the role of staphylococcal enterotoxin B (SEB) on the differentiation of Tregs to RORC+Tregs in vitro. Methods: A total of 60 patients were enrolled in this study. Of the 60 patients, 40 had chronic rhinosinusitis with nasal polyps (CRSwNPs), and 20 subjects who were undergoing septoplasty were enrolled as control subjects. The nasal polyps of CRSwNP patients were subclassified as either eosinophilic polyp (EP) and noneosinophilic polyp (NEP) according to the result of hematoxylin and eosin stain. Tissues and whole blood were collected from all subjects. Double immunofluorescent staining and reverse-transcription polymerase chain reaction for RORC and FOXP3 were conducted on the tissues. RORC expressions of Tregs were measured in the tissue using flow cytometry. The proportions of RORC+Tregs subsets and cytokines profiles from the supernatant were measured using flow cytometry after stimulation with SEB. Results: The cells that express both RORC and FOXP3 and RORC+Tregs were significantly higher in the nasal polyps, especially in EPs compared with NEPs, and control mucosa. RORC+Tregs in peripheral blood mononuclear cells significantly increased in patients with EPs 24 hours after SEB stimulation in vitro. Conclusion: The results indicate that SEB may be involved in the differentiation of Tregs to RORC+Tregs, and these cells may be involved in the pathogenesis of eosinophilic nasal polyposis. [ABSTRACT FROM AUTHOR]

Diverse immune cells contribute to the pathogenesis of chronic rhinosinusitis (CRS), an inflammatory disease of the nasal cavity and paranasal sinuses. However, whether mucosal-associated invariant T (MAIT) cells are present in human sinonasal tissues remains unclear. Furthermore, the characteristics of sinonasal MAIT cells have not been studied in patients with CRS. We investigated the phenotype, function, and clinical implications of MAIT cells in patients with CRS. Peripheral blood and sinonasal tissue were obtained from patients with CRS with (CRSwNP) or without nasal polyps (CRSsNP) and healthy controls. MAIT cells were analyzed by flow cytometry. We found that MAIT cells are present in human sinonasal tissues from healthy controls and patients with CRS. The sinonasal MAIT cell population, but not peripheral blood MAIT cells, from patients with CRSsNP, noneosinophilic CRSwNP (NE-NP), or eosinophilic CRSwNP (E-NP) had a significantly higher frequency of activated cells marked by CD38 expression. In functional analysis, the sinonasal MAIT cell population from NE-NP and E-NP had a significantly higher frequency of IL-17A+ cells but lower frequency of IFN-γ+ or TNF+ cells than control sinonasal tissues. Furthermore, CD38 expression and IL-17A production by sinonasal MAIT cells significantly correlated with disease extent evaluated by the Lund-Mackay computed tomography score in patients with E-NP. Sinonasal MAIT cells exhibit an activated phenotype and produce higher levels of IL-17A in patients with CRSwNP. These alterations are associated with the extent of disease in patients with E-NP. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: The pathogenesis of chronic rhinosinusitis with nasal polyposis (CRSwNP) is still unclear. To evaluate the role of regulatory T cells (Treg) in the pathogenesis of nasal polyposis, we tested migration potential of Treg purified from subjects with CRSwNP, CRS without NP and controls. The nasal tissue expressions of FOXP3 were analyzed by means of RT-PCR and double immunohistochemistry. Chemotaxis assays were used to evaluate the migration potential of Treg onto bronchial epithelial cells and primary nasal epithelial cells, and toward chemokines. FOXP3+CD3+ cells frequency and FOXP3 transcript expression in nasal tissue, and migration potentials of Treg toward airway epithelial cells and CCL1 were significantly lower in CRSwNP compared with other groups (P <0.05). These results indicate that migration potential of Treg is decreased in CRSwNP subjects, and this may be one of the reasons why tissue infiltration of Treg was decreased as seen in the immunohistochemistry of nasal polyps from CRSwNP subjects. [ABSTRACT FROM AUTHOR]

Background: Nasal polyposis is characterized by persistent inflammation and remodeling in sinonasal mucosa. Toll‐like receptor 9 (TLR9) is a DNA receptor of the innate immune system that plays a pivotal role in fibrosis and inflammatory responses. The aim of this study is to explore the expression, activity, and potential pathogenic role of TLR9 signaling in tissue remodeling in nasal polyp–derived fibroblasts (NPDFs). Methods: Fibrotic and inflammatory responses elicited by type A CpG oligonucleotides were examined in the NPDFs by a combination of real‐time quantitative polymerase chain reaction, Western blot analysis, enzyme‐linked immunosorbent assay, and immunofluorescence staining. For these experiments, the NPDFs were stimulated with different TLR9 agonists (CpG A and B) and blocked with inhibitors (MyD88 inhibitor and chloroquine). Results: TLR9 expression was significantly higher in nasal polyposis (NP) tissues compared to control or chronic rhinosinusitis (CRS) mucosa. In the NPDFs, TLR9 showed intracellular localization and expression of TLR9 was increased after treatment with CpG A. CpG A increased production of α‐smooth muscle actin (α‐SMA), fibronectin, and matrix metalloproteinases (MMPs) (MMP1, MMP2, and MMP9) in the NPDFs, while MyD88 inhibitor and chloroquine, which are known to block the TLR9 signaling pathway, inhibited their production. CpG A also produced type I interferons (IFN‐α and IFN‐β), which were inhibited by MyD88 inhibitor. Conclusion: Our data indicates that CpG A–induced fibroblast activation and cytokine production were mediated via TLR9 stimulation in NPDFs. Disrupting this process with an inhibitor targeting TLR9 or its downstream signaling pathways could represent a novel approach to CRS with NP (CRSwNP) therapy. [ABSTRACT FROM AUTHOR]

Background Sinonasal fungus ball (FB) is a type of noninvasive fungal rhinosinusitis affecting immunocompetent hosts. FB, previously considered rare, has been reported with increasing frequency. We reviewed our experience of 538 cases over the past 20 years. Methods We retrospectively examined clinical records including clinical presentations, radiological findings, management, and outcomes of FB patients who have undergone surgery for treatment. The number of FB patients who underwent endoscopic sinus surgery (ESS) was calculated annually. Causal relationships between structural variations and FB were also investigated. Results The number of FB patients who underwent sinus surgery has increased. The mean age was 58.3 years, and the gender ratio was approximately 2 (female): 1 (male). While the most common presenting symptoms of maxillary sinus FB patients were nasal symptoms, such as postnasal drip and nasal obstruction, sphenoid sinus FB patients presented with headache mostly. On computed tomography (CT) scans, the most common finding was intralesional hyperdensity (77.3%). There was no significant correlation between the presence of FB and structural variations (nasal septal deviation, concha bullosa, Haller cell). Median follow-up period of the patients was 11 months. Recurrence or residual disease occurred in only 6 (1.1%) cases. Conclusion The number of FB patients who underwent surgery has increased steadily over the past 20 years. FB should be considered in patients with unilateral nasal symptoms and unexplained headaches. A preoperative CT scan is an essential tool in making diagnosis easier and faster. Endoscopic surgery is the treatment of choice, with a low morbidity and recurrence rate. [ABSTRACT FROM AUTHOR]