Aberrant Activation of Heat Shock Protein 60/65 Reactive T Cells in Patients with Behcet’s Disease

Figure 3

A schematic representation of skewed Th17/Treg cell differentiation in patients with BD, a hypothesis. TGFβ activates Smad pathway via TGFβ receptor I/II complex, and activated Smad protein leads to forkhead box P3 (Foxp3) expression which is a master gene of Treg cells [27]. TGFβ also activates p38 mitogen-activated protein kinase (MAPK) which regulates Th17 cell differentiation [32, 33]. In the presence of TGFβ, IL-6/STAT3 signaling pathway plays a critical role in the reduction of Foxp3 expression and in the induction of retinoic acid receptor-related orphan receptor C (RORC) expression which is a master gene of Th17 cells [34]. In patients with BD, monocytes and T cells overproduce IL-6 in the presence of HSP [41]. Overexpression of RORC [42, 43], underexpression of Foxp3 [44, 45], and higher frequencies of Th17 cells [42–44, 46] are reported in patients with BD. PHA: phytohemagglutinin, TGFβRI/II: TGFβ receptor types I and II, STAT3: signal transducer and activator of transcription 3.