An increase of CD83+ dendritic cells ex vivo correlates with increased regulatory T cells in patients with active eosinophilic granulomatosis and polyangiitis

Abstract

BackgroundEosinophilic 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.ResultsThe 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.ConclusionThe 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.

Innate immune response reflects disease activity in eosinophilic granulomatosis with polyangiitis

“…51 In addition, we have reported that the percentage of CD83 + dendritic cells, which are mature dendritic cells, was significantly correlated with the number of naturally occurring or inducible T reg cells (CD4 + CD25 + T cells producing IL-10) or the number of TGF-β cells, but not the number of eosinophils in patients with EGPA. 52 We have also reported that the amount of CD80 + , CD27 + , or CD95 + expressed on CD19 + B cells was increased in some patients with EGPA, especially in those who experienced more frequent relapses than in those who sel- 27 In the present study, we had detected more CD4 + T cells producing IL-25 in peripheral blood in patients with EGPA at relapse than in those at remission or in patients with BA, although the difference was very small.…”

High Levels of Regulatory T Cells in Blood Are a Poor Prognostic Factor in Patients With Diffuse Large B-Cell Lymphoma

“…Another possibility is that the increased Tregs mediated by tolerogenic DCs suppress the antitumor response generated by effector lymphocytes. 16,45 Recently, others have reported that inhibition of p38 mitogen-activated protein kinase in DCs overcomes Treg-mediated immunosuppression and prompts antitumor immune responses. 46 These findings may help improve DC-based immunotherapy.…”

“…15 Tregs function by a direct cell contact manner and produce transforming growth factor-β (TGF-β) and IL-10 and can be separated into two forms: "natural" Tregs (Foxp3+CD4+), which originate in the thymus, and "induced" Tregs (CD25+CD4+), which are derived from naive T cells in the periphery. 16 They are similar, both phenotypically and functionally, but are reported to be different in "Helio" expression, which is a zinc finger transcription factor. 17 Inducible Tregs are derived from naive T cells by costimulation with T-cell receptors and TGF-β.…”

Pulmonary Eosinophilic Granulomatosis with Polyangiitis Has IgG4 Plasma Cells and Immunoregulatory Features

“…Except for a study of CD83 and CD208, 17 this is, to our knowledge, the first immunostaining study of lung tissue in EGPA. This is the first lung tissue transcriptome study in EGPA.…”