<p>IL-17A and IFN-? are Up-regulated in CD4 and ?d T Cells in Active Behcet's Disease Patients</p>

Involvement of gamma delta T cells is implicated in the pathogenesis of Behcet'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-gamma. Mainly CD4(+) T cells are investigated previously for the production of these inflammatory cytokines. In this study, the role of gamma delta 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 gamma delta T cells were compared in ex vivo samples collected from patients with BD and healthy controls (HC).& nbsp;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 gamma delta and CD4(+) T cells. IFN-gamma, IL-17A, IL-22, as well as CD107a (LAMP1) and CD16 (Fc gamma RIII) were evaluated in both cell subtypes after in vitro stimulation.& nbsp;Only IFN-gamma production was increased in gamma delta T cells of a-BD patients. There was no difference in increase of CD107a or decrease of CD16 surface expression on gamma delta T cells upon stimulation between the groups. Ex vivo IL-17A and both IL-17A/IFN-gamma production and expression of CD161, CCR6 by CD4(+) T cells were increased in a-BD.& nbsp;Along with CD4(+) T cells, gamma delta T cells have complementary roles in cytokine production in BD. Higher IFN-gamma production of gamma delta T cells suggests the role of an environmental triggers in BD pathogenesis, whereas IL-17 related activity is mainly provided by CD4(+) T cells

Pathogenesis of Behcet's Syndrome: Genetic, Environmental and Immunological Factors

Behcet's syndrome (BS) is a rare systemic vasculitis, characterized by a wide range of different clinical involvements and unpredictable phases of recurrence and remission. BS can be described as a multifactorial disease with an incompletely known etiopathogenesis; in fact, though presenting some peculiar features, such as its typical geographic distribution and the strong association with the well-known genetic predisposing factor HLA-B*51, the cause behind the onset and progression of the disease remains currently not fully understood. Besides genetic HLA and non-HLA predisposing associations and epigenetic influence, environmental factors also play an important role in the pathogenesis of the disease, and among these, infectious agents (both bacterial and viral) and specific microbiome alterations are considered of particular relevance in BS pathogenesis. BS has been included for decades among autoimmune diseases, in light of evidence showing T- and B-cell aberrant responses. However, because of recurrent mucocutaneous lesions and episodes of inflammation without antigen-specific T-cell or autoantibody responses, BS has also been classified among autoinflammatory disorders. Nevertheless, differently from autoinflammatory diseases, BS mildly responds to therapies targeting IL-1, its onset is not usually in childhood, and has high neutrophilic vasculitic involvement. Finally, given the association with HLA class I alleles, similar to spondyloarthropathies, the concept of BS as a major histocompatibility complex (MHC) I -opathy has been introduced. Understanding the complex etiopathogenesis of BS is essential to identify modifiable risk factors of BS occurrence or exacerbation and to develop targeted therapies. This review summarizes current evidence on the main genetic, environmental and immunological factors contributing to BS development