title: Peripheral blood and tissue T regulatory cells in chronic rhinosinusitis.
abstract: 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-β1) and higher levels of proinflammatory cytokines (TNF-α and IL-6) were found from PBMCs from CRS subjects compared with  controls (p < 0.05).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Section of Otolaryngology-Head and Neck Surgery, Department of Surgery, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Shilpy
authors.initials: S
authors.lastname: Sharma
authors.forename: So
authors.initials: S
authors.lastname: Watanabe
authors.forename: Anita
authors.initials: A
authors.lastname: Sivam
authors.forename: JiangHong
authors.initials: J
authors.lastname: Wang
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Neuwirth
authors.forename: Rosanne I
authors.initials: RI
authors.lastname: Perez
authors.forename: Marcella
authors.initials: M
authors.lastname: De Tineo
authors.forename: Fuad M
authors.initials: FM
authors.lastname: Baroody
authors.forename: Robert M
authors.initials: RM
authors.lastname: Naclerio
authors.forename: Jayant M
authors.initials: JM
authors.lastname: Pinto
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D001775:Blood Circulation / Q000276:immunology; D002469:Cell Separation; D002478:Cells, Cultured; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D010256:Paranasal Sinuses / Q000276:immunology*; D012220:Rhinitis / Q000097:blood* / Q000276:immunology*; D012852:Sinusitis / Q000097:blood* / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D016207:Cytokines