title: Evidence supporting a protective role for th9 and th22 cytokines in human and experimental periapical lesions.
abstract: BACKGROUND
  The development of periapical granulomas is dependent on the host response and involves Th1, Th2, Th17, and Treg-related cytokines. The discovery of new Th9 and Th22 subsets, with important immunomodulatory roles mediated by interleukin (IL)-9 and IL-22, respectively, emphasizes the need for reevaluation of current cytokine paradigms in context of periapical lesions. We investigated the expression of IL-9 and IL-22 in active and stable human granulomas and throughout experimental lesion development in mice.
  
  
  METHODS
  Periapical granulomas (N = 83) and control specimens (N = 24) were evaluated regarding the expression of IL-9 and IL-22 via real-time polymerase chain reaction. Experimental periapical lesions were induced in mice (pulp exposure and bacterial inoculation) and the lesions evolution correlation with IL-9 and IL-22 expression kinetics was evaluated.
  
  
  RESULTS
  IL-9 and IL-22 mRNA expression was higher in periapical lesions than in control samples; higher levels of IL-9 and IL-22 were observed in inactive than in active lesions. In the experimental lesions model, increasing levels of IL-9 and IL-22 mRNA were detected in the lesions, and inverse correlations were found between IL-9 and IL-22 and the increase of lesion area in the different time point intervals.
  
  
  CONCLUSIONS
  Our results suggest that Th9 and Th22 pathways may contribute to human and experimental periapical lesion stability.
authors.affiliation: Department of Biological Sciences, School of Dentistry of Bauru, University of São Paulo (FOB/USP), Bauru, São Paulo, Brazil.
authors.forename: Andreza Maria Fabio
authors.initials: AM
authors.lastname: Aranha
authors.forename: Carlos Eduardo
authors.initials: CE
authors.lastname: Repeke
authors.forename: Thiago Pompermaier
authors.initials: TP
authors.lastname: Garlet
authors.forename: Andreia Espindola
authors.initials: AE
authors.lastname: Vieira
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Campanelli
authors.forename: Ana Paula Favaro
authors.initials: AP
authors.lastname: Trombone
authors.forename: Ariadne
authors.initials: A
authors.lastname: Letra
authors.forename: Renato Menezes
authors.initials: RM
authors.lastname: Silva
authors.forename: Gustavo Pompermaier
authors.initials: GP
authors.lastname: Garlet
mesh_terms: D000196:Actinomycosis / Q000276:immunology; D000293:Adolescent; D000328:Adult; D000818:Animals; D016866:Bacteroidaceae Infections / Q000276:immunology; D003789:Dental Pulp Exposure / Q000276:immunology / Q000382:microbiology; D004195:Disease Models, Animal; D005260:Female; D005674:Fusobacterium Infections / Q000276:immunology; D016967:Fusobacterium nucleatum / Q000276:immunology; D006801:Humans; D056747:Immunomodulation / Q000276:immunology; D016906:Interleukin-9 / Q000276:immunology*; D007378:Interleukins / Q000276:immunology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D053244:Osteoprotegerin / Q000032:analysis; D010484:Periapical Granuloma / Q000276:immunology*; D016966:Porphyromonas gingivalis / Q000276:immunology; D045242:Prevotella nigrescens / Q000276:immunology; D053245:RANK Ligand / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D055815:Young Adult; D000097043:Interleukin-22
chemical_list: D016906:Interleukin-9; D007378:Interleukins; D053244:Osteoprotegerin; D053245:RANK Ligand; D000097043:Interleukin-22; C508607:IL9 protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human