Peripheral blood and tissue T regulatory cells in chronic rhinosinusitis

Background: The pathogenesis of chronic rhinosinusitis (CRS) has not been fully elucidated. Increased inflammatory cell infiltration and decreased numbers and/or impaired function of T regulatory cells (Tregs) have been reported. This study aimed to determine the role of Tregs in CRS in peripheral blood (PB) and sinus tissue. Methods: Sinus tissue was obtained from 16 CRS subjects and 5 controls. PB from additional 16 CRS subjects and total 20 controls was obtained. Immunohistochemical analysis (CD3(+), CD4(+), CD8(+), and Treg [CD4(+)-FoxP3(+) and CD25(+)-FoxP3(+)] cells) of sinus tissue was performed. Percentage of PB Tregs (CD4(+)-CD25(+)-FoxP3(+) cells) was analyzed by flow cytometry. Spontaneous and phytohemagglutinin (PHA)-induced release of cytokines (IL-6, IL-4, IL-10, interferon gamma, transforming growth factor [TGF] beta1, and TNF-alpha) from PB mononuclear cells (PBMCs) was determined. Results: PB flow cytometric analysis revealed a lower percentage of Tregs in subjects with CRS compared with healthy controls (p = 0.0003). Although no differences in the PB Treg counts were observed between the CRS subjects with nasal polyposis (CRSwNP) and without nasal polyposis (CRSsNP), immunohistochemical analysis performed on sinus tissue revealed a higher proportion of Tregs in CRSwNP subjects compared with CRSsNP (p < 0.05). Additionally, we failed to detect any Tregs from control sphenoid sinus tissue. Lower levels of regulatory cytokines (IL-10 and TGF-beta 1) and higher levels of proinflammatory cytokines (TNF-alpha and IL-6) were found from PBMCs from CRS subjects compared with controls (p < 0.05). Conclusion: Our findings suggest that CRS subjects exhibit a decreased percentage of PB Tregs compared with normal controls. PBMCs from CRS subjects show a more proinflammatory and less regulatory phenotype. (Am J Rhinol Allergy 26, 371-379, 2012; doi: 10.2500/ajra.2012.26.3800)