title: Interleukin-21 contributes to germinal centre formation and immunoglobulin G4 production in IgG4-related dacryoadenitis and sialoadenitis, so-called Mikulicz's disease.
abstract: OBJECTIVE
  Interleukin (IL)-21 is mainly produced by CD4 T helper (Th) cells including Th2, Th17 and follicular helper T (Tfh) cells. Recent studies have reported that IL-21 is involved in the formation of germinal centres (GCs) and class switching of IgG4. It has been suggested that IgG4-related dacryoadenitis and sialoadenitis (IgG4-DS), so-called Mikulicz's disease (MD), is distinct from Sjögren's syndrome (SS) and shows a high frequency of GC formation in salivary glands. In this study the expression of IL-21 in IgG4-DS and SS patients was examined.
  
  
  METHODS
  Twelve patients with IgG4-DS, 15 with SS and 15 healthy subjects were screened for (1) ectopic GC formation in formalin-fixed labial salivary gland (LSG) biopsy samples; (2) expression of IL-21, Th2-, Th17- and Tfh-related molecules (cytokines, chemokine receptors and transcription factors) in LSGs; (3) relationship between IgG4/IgG ratio and mRNA expression of IL-21 in LSGs.
  
  
  RESULTS
  mRNA expression of IL-21 and Bcl-6 in LSGs from patients with IgG4-DS was significantly higher than in patients with SS and controls. IL-21 and CXCR5 were detected by immunohistochemistry in or around GC in patients with SS and those with IgG4-DS. IL-21 was detected in infiltrating lymphocytes outside GC only in patients with IgG4-DS. Expression of IL-21 was consistent with that of Th2-related molecules while IL-17 was rarely seen in IgG4-DS. Furthermore, the expression of IL-21 in LSGs was correlated with the number of GC formations and the IgG4/IgG ratio in patients with IgG4-DS.
  
  
  CONCLUSIONS
  These results suggest that overexpression of IL-21 by Th2 cells might play a key role in GC formation and IgG4 production in IgG4-DS.
authors: Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
authors: Takashi
authors: T
authors: Maehara
authors: Masafumi
authors: M
authors: Moriyama
authors: Hitoshi
authors: H
authors: Nakashima
authors: Katsuhisa
authors: K
authors: Miyake
authors: Jun-Nosuke
authors: JN
authors: Hayashida
authors: Akihiko
authors: A
authors: Tanaka
authors: Shouichi
authors: S
authors: Shinozaki
authors: Yoshiaki
authors: Y
authors: Kubo
authors: Seiji
authors: S
authors: Nakamura
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D003607:Dacryocystitis / Q000276:immunology* / Q000473:pathology; D005260:Female; D018858:Germinal Center / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008882:Mikulicz' Disease / Q000276:immunology* / Q000473:pathology; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000276:immunology; D051560:Proto-Oncogene Proteins c-bcl-6; D051257:Proto-Oncogene Proteins c-maf / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D054398:Receptors, CCR4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D054380:Receptors, CXCR5 / Q000235:genetics / Q000276:immunology; D012469:Salivary Glands / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012793:Sialadenitis / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology; D000098546:Interleukin-21
chemical_list: C084103:BCL6 protein, human; C515354:CCR4 protein, human; C095085:CXCR5 protein, human; D004268:DNA-Binding Proteins; C508717:IL17A protein, human; C508598:IL4 protein, human; D007074:Immunoglobulin G; D020381:Interleukin-17; D007378:Interleukins; C495607:MAF protein, human; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D051560:Proto-Oncogene Proteins c-bcl-6; D051257:Proto-Oncogene Proteins c-maf; D012333:RNA, Messenger; D054398:Receptors, CCR4; D054380:Receptors, CXCR5; D015847:Interleukin-4; D000098546:Interleukin-21