IL-17A and IFN-γ are Up-regulated in CD4 and γδ T Cells in Active Behcet's Disease Patients

Abstract

Involvement of γδ T cells is implicated in the pathogenesis of Behçet's disease (BD) as a bridge between innate and adaptive responses. IL-17 and IL-22 have also been shown to participate in the BD pathogenesis in addition to IFN-γ. Mainly CD4⁺ T cells are investigated previously for the production of these inflammatory cytokines. In this study, the role of γδ T cells in cytokine-related mechanisms was evaluated in BD in comparison to CD4⁺ T cells. Surface expression of markers for functional states of both CD4⁺ and γδ T cells were compared in ex vivo samples collected from patients with BD and healthy controls (HC). Sixteen active BD (a-BD), 9 inactive BD (i-BD) patients and 25 HC were investigated. The expression of CD161, CCR6 as markers for IL-17 producing cells were analyzed on γδ and CD4⁺ T cells. IFN-γ, IL-17A, IL-22, as well as CD107a (LAMP1) and CD16 (FcγRIII) were evaluated in both cell subtypes after in vitro stimulation. Only IFN-γ production was increased in γδ T cells of a-BD patients. There was no difference in increase of CD107a or decrease of CD16 surface expression on γδ T cells upon stimulation between the groups. Ex vivo IL-17A and both IL-17A/IFN-γ production and expression of CD161, CCR6 by CD4⁺ T cells were increased in a-BD. Along with CD4⁺ T cells, γδ T cells have complementary roles in cytokine production in BD. Higher IFN-γ production of γδ T cells suggests the role of an environmental triggers in BD pathogenesis, whereas IL-17 related activity is mainly provided by CD4⁺ T cells.

Keywords: Behçet's disease; IL-17, IFN-γ; T helper cells; γδ T cell.