Role of staphylococcal enterotoxin B on the differentiation of regulatory T cells in nasal polyposis

Background: The pathogenesis of nasal polyposis has not been fully understood. Recent studies indicate that there is a subset of CD4(+) CD25(high) FoxP3(+) 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.