title: Factors involved in the T helper type 1 and type 2 cell commitment and osteoclast regulation in inflammatory apical diseases.
abstract: BACKGROUND
  Periapical chronic lesion formation involves activation of the immune response and alveolar bone resorption around the tooth apex. However, the overall roles of T helper type 1 (Th1), Th2, and T-regulatory cell (Treg) responses and osteoclast regulatory factors in periapical cysts and granulomas have not been fully determined. This study aimed to investigate whether different forms of apical periodontitis, namely cysts and granulomas, show different balances of Th1, Th2 regulators, Treg markers, and factors involved in osteoclast chemotaxis and activation.
  
  
  METHODS
  Gene expression of these factors was assessed using quantitative real-time polymerase chain reaction, in samples obtained from healthy gingiva (n = 8), periapical granulomas (n = 20), and cysts (n = 10).
  
  
  RESULTS
  Periapical cysts exhibited a greater expression of GATA-3, while a greater expression of T-bet, Foxp3, and interleukin-10 (IL-10) was seen in granulomas. The expression of interferon-gamma, IL-4, and transforming growth factor-beta was similar in both lesions. Regarding osteoclastic factors, while the expression of SDF-1alpha/CXCL12 and CCR1 was higher in cysts, the expression of RANKL was significantly higher in granulomas. Both lesions exhibited similar expression of CXCR4, CKbeta8/CCL23, and osteoprotegerin, which were significantly higher than in control.
  
  
  CONCLUSIONS
  Our results showed a predominance of osteoclast activity in granulomas that was correlated with the Th1 response. The concomitant expression of Treg cell markers suggests a possible suppression of the Th1 response in granulomas. On the other hand, in cysts the Th2 activity is augmented. The mechanisms of periradicular lesion development are still not fully understood but the imbalance of immune and osteoclastic cell activity in cysts and granulomas seems to be critically regulated by Treg cells.
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: S Y
authors.initials: SY
authors.lastname: Fukada
authors.forename: T A
authors.initials: TA
authors.lastname: Silva
authors.forename: G P
authors.initials: GP
authors.lastname: Garlet
authors.forename: A L
authors.initials: AL
authors.lastname: Rosa
authors.forename: J S
authors.initials: JS
authors.lastname: da Silva
authors.forename: F Q
authors.initials: FQ
authors.lastname: Cunha
mesh_terms: D000328:Adult; D016301:Alveolar Bone Loss / Q000276:immunology / Q000378:metabolism; D054405:Chemokine CCL3 / Q000096:biosynthesis; D054377:Chemokine CXCL12 / Q000096:biosynthesis; D019742:Chemokines, CC / Q000096:biosynthesis; D002633:Chemotaxis; D002908:Chronic Disease; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D050990:GATA3 Transcription Factor / Q000096:biosynthesis; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D008875:Middle Aged; D010010:Osteoclasts / Q000502:physiology*; D053244:Osteoprotegerin / Q000096:biosynthesis; D010484:Periapical Granuloma / Q000276:immunology* / Q000378:metabolism; D053245:RANK Ligand / Q000096:biosynthesis; D011842:Radicular Cyst / Q000276:immunology* / Q000378:metabolism; D054389:Receptors, CCR1 / Q000096:biosynthesis; D019718:Receptors, CXCR4 / Q000096:biosynthesis; D020825:T-Box Domain Proteins / Q000096:biosynthesis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D000098815:T-bet Transcription Factor
chemical_list: C105504:CCL23 protein, human; C515255:CXCL12 protein, human; D054405:Chemokine CCL3; D054377:Chemokine CXCL12; D019742:Chemokines, CC; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D053244:Osteoprotegerin; D053245:RANK Ligand; D054389:Receptors, CCR1; D019718:Receptors, CXCR4; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D016753:Interleukin-10; D007371:Interferon-gamma