Title:A Possible Role for Interleukin 37 in the Pathogenesis of Behcet's Disease
VOLUME: 14 ISSUE: 4
Author(s):Z. Ye, C. Wang, A. Kijlstra, X. Zhou and P. Yang
Affiliation:The First Affiliated Hospital of Chongqing Medical University, Youyi Road 1, Chongqing, 400016, P.R. China.
Keywords:Behcet's disease, cytokine, dendritic cells, IL-37, inflammatory response, MAPK family, reactive oxygen
species, uveitis.
Abstract: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-1β and TNF-α, 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.
