A Possible Role for Interleukin 37 in the Pathogenesis of Behcet's Disease

Interleukin 37 has been found to play a significant regulatory role in the innate immune response. It is not yet known whether IL-37 has also been involved in the development of Behcet's disease (BD), a chronic systemic inflammatory disease. To examine the role of IL-37 in the pathogenesis of BD, a number of experiments were performed. IL-37 expression in peripheral blood mononuclear cells (PBMCs) from BD patients and normal controls was measured by RT-PCR and flow cytometry. Monocyte-derived Dendritic Cells (DCs) were cultured with or without IL-37 and levels of cytokines in the culture supernatants were measured by ELISA. The DC surface markers, reactive oxygen species (ROS) production and mitogen-activated protein kinase (MAPK) activation were measured by flow cytometry. The effect of IL-37-treated DCs on the development of CD4(+) T cells was measured by ELISA and flow cytometry. The results show that both IL-37 mRNA level and protein expression were significantly decreased in PBMCs from active BD patients compared to normal controls. DCs stimulated with rIL-37 showed a decreased expression of IL-6, IL-1 beta and TNF-alpha, and a higher production of IL-27. rIL-37 significantly inhibited the production of ROS by DCs and reduced the activation of ERK1/2, JNK and P38 MAPK in DCs. rIL-37-treated DCs remarkably inhibited Th17 and Th1 cell responses as compared to control DCs. rIL-37 did not affect the expression of DC surface markers (CD40, CD86, CD80 and HLA-DR) or IL-10 production by DCs. We conclude that a decreased IL-37 expression in active BD patients may trigger the production of pro-inflammatory cytokines and ROS in association with activation of Th1 and Th17 cells by DCs.