title: An increase of CD83+ dendritic cells ex vivo correlates with increased regulatory T cells in patients with active eosinophilic granulomatosis and polyangiitis.
abstract: BACKGROUND
  Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare disease characterized by the presence of allergic granulomatosis and necrotizing vasculitis with eosinophilic infiltration. The etiology of EGPA is unknown. Dendritic cells (DCs) are not only critical for the induction of primary immune responses; they may also be important for the induction of immunological tolerance and the regulation of the type of T-cell-mediated immune response. To investigate whether DC maturation is associated with EGPA disease status, we examined the relationship between the maturation of DCs and the differentiation of regulatory T (Treg) cells in EGPA patients. We exposed the CD14+ blood monocytes of 19 patients with EGPA in remission or relapse to stimulation with GM-CSF and IL-4 for 6 d and lipopolysaccharide for 24 h to obtain mature CD83+ DCs and immature CD206+ DCs. Using immunohistochemistry, we examined four patients for the presence of CD83+ and CD206+ DCs in the lung at the onset of EGPA.
  
  
  RESULTS
  The percentage of CD83+ cells among DCs differentiated from CD14+ monocytes was lower for EGPA patients in relapse than in remission. The percentage of CD83+ DCs was inversely correlated with the percentage of CD206+ DCs and was significantly correlated with the numbers of naturally occurring CD4+ regulatory Treg (nTreg; FOXP3+CD4+) cells and inducible Treg (iTreg; CD4+CD25+ T cells producing IL-10 or TGF-β) cells but not the number of eosinophils. The percentage of CD206+ DCs was significantly inversely correlated with the percentages of nTreg and iTreg cells but not the number of eosinophils. Immunohistochemistry revealed both CD206+ DCs and CD83+ DCs in alveoli and interstitial spaces at the onset of EGPA.
  
  
  CONCLUSIONS
  The maturation of DCs from monocytes was related to disease activity in patients with EGPA. Increased CD83+ DCs in EGPA patients may induce the differentiation of iTreg and nTreg cells, thereby suppressing inflammation and disease activity.
authors.affiliation: Departments of Allergy and Respirology, 18-1 Sakuradai, Minami-ku Sagamihara 252-0392, Kanagawa, Japan. n-tsurikisawa@sagamihara-hosp.gr.jp.
authors.forename: Naomi
authors.initials: N
authors.lastname: Tsurikisawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saito
authors.forename: Chiyako
authors.initials: C
authors.lastname: Oshikata
authors.forename: Takahiro
authors.initials: T
authors.lastname: Tsuburai
authors.forename: Miyako
authors.initials: M
authors.lastname: Ishiyama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mitomi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Akiyama
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D001706:Biopsy; D002452:Cell Count; D002454:Cell Differentiation / Q000276:immunology; D015267:Churg-Strauss Syndrome / Q000276:immunology* / Q000473:pathology; D003713:Dendritic Cells / Q000473:pathology*; D004803:Eosinophilic Granuloma / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000096:biosynthesis; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology; D012008:Recurrence; D012074:Remission Induction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D007136:Immunoglobulins; D016753:Interleukin-10; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen