title: Increased levels of the T-helper 22-associated cytokine (interleukin-22) and transcription factor (aryl hydrocarbon receptor) in patients with periodontitis are associated with osteoclast resorptive activity and severity of the disease.
abstract: OBJECTIVE
  Two new T-helper (Th) phenotypes have been recently described and named Th9 and Th22 lymphocytes; however, their role in the pathogenesis of periodontitis remains unclear. This study was aimed to assess whether Th9 and Th22 lymphocytes, through interleukin (IL)-9 and IL-22 production, respectively, are associated with the severity of periodontitis and bone resorption.
  
  
  METHODS
  Gingival crevicular fluid samples and biopsies were obtained from patients with moderate-to-advanced chronic periodontitis and gingivitis, and healthy controls. The levels for the Th9 and Th22-associated cytokines and master-switch transcription factors Spi-B and aryl hydrocarbon receptor (AhR) were quantified by enzyme-linked immunosorbent assay, real-time reverse-transcription quantitative polymerase chain reaction and flow cytometry. In addition, the osteoclast activity in response to tissue homogenates from periodontitis and healthy samples was analyzed quantifying the number of TRAP-positive cells and areas of bone resorption pits produced, in the presence or absence of recombinant human IL-22 and anti-IL-22 neutralization antibody.
  
  
  RESULTS
  Higher levels of IL-22 and AhR were detected in patients with periodontitis compared with gingivitis and healthy individuals. In addition, higher levels of IL-9 and Spi-B were detected in gingivitis patients compared with periodontitis and healthy individuals. In patients with periodontitis, a significant positive correlation was detected between secreted levels of IL-22 and clinical attachment level of the sampled periodontal pockets. When osteoclasts were exposed to tissue homogenates obtained from patients with periodontitis, higher levels of resorptive activity were observed as compared with the same cells exposed to tissue homogenates obtained from healthy individuals, and this increment was dependent on the presence and neutralization of IL-22.
  
  
  CONCLUSIONS
  Increased levels of IL-22 produced by Th22 lymphocytes are associated with the pathogenesis of periodontitis, in particular, with osteoclast resorptive activity and severity of disease.
authors.affiliation: Periodontal Biology Laboratory, Faculty of Dentistry, Universidad de Chile, Santiago, Chile.|Department of Conservative Dentistry, Faculty of Dentistry, Universidad de Chile, Santiago, Chile.
authors.forename: J
authors.initials: J
authors.lastname: Díaz-Zúñiga
authors.affiliation: Periodontal Biology Laboratory, Faculty of Dentistry, Universidad de Chile, Santiago, Chile.|Department of Conservative Dentistry, Faculty of Dentistry, Universidad de Chile, Santiago, Chile.
authors.forename: S
authors.initials: S
authors.lastname: Melgar-Rodríguez
authors.affiliation: Periodontal Biology Laboratory, Faculty of Dentistry, Universidad de Chile, Santiago, Chile.
authors.forename: L
authors.initials: L
authors.lastname: Rojas
authors.affiliation: Periodontal Biology Laboratory, Faculty of Dentistry, Universidad de Chile, Santiago, Chile.
authors.forename: C
authors.initials: C
authors.lastname: Alvarez
authors.affiliation: Periodontal Biology Laboratory, Faculty of Dentistry, Universidad de Chile, Santiago, Chile.
authors.forename: G
authors.initials: G
authors.lastname: Monasterio
authors.affiliation: Department of Conservative Dentistry, Faculty of Dentistry, Universidad de Chile, Santiago, Chile.
authors.forename: P
authors.initials: P
authors.lastname: Carvajal
authors.affiliation: Periodontal Biology Laboratory, Faculty of Dentistry, Universidad de Chile, Santiago, Chile.|Dentistry Unit, Faculty of Health Sciences, Universidad Autónoma de Chile, Santiago, Chile.
authors.forename: R
authors.identifier: http://orcid.org/0000-0002-1391-320X
authors.initials: R
authors.lastname: Vernal
mesh_terms: D000328:Adult; D055113:Chronic Periodontitis / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D005883:Gingival Crevicular Fluid / Q000737:chemistry*; D005891:Gingivitis / Q000276:immunology / Q000473:pathology; D006801:Humans; D016906:Interleukin-9 / Q000032:analysis / Q000378:metabolism; D007378:Interleukins / Q000032:analysis / Q000378:metabolism*; D008297:Male; D010010:Osteoclasts / Q000276:immunology* / Q000378:metabolism*; D017622:Periodontal Attachment Loss; D010514:Periodontal Pocket / Q000276:immunology; D012313:RNA / Q000302:isolation & purification; D012337:RNA, Ribosomal, 18S / Q000032:analysis; D018336:Receptors, Aryl Hydrocarbon / Q000032:analysis / Q000378:metabolism*; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D016207:Cytokines; D004268:DNA-Binding Proteins; D016906:Interleukin-9; D007378:Interleukins; D012313:RNA; D012337:RNA, Ribosomal, 18S; D018336:Receptors, Aryl Hydrocarbon; D014157:Transcription Factors; D000097043:Interleukin-22; C076877:SPIB protein, human
keywords: AhR, transcription factor aryl hydrocarbon receptor; Th22 lymphocytes; bone resorption; interleukin-22; periodontitis