Interleukin-33 augments Treg cell levels: a flaw mechanism in atherosclerosis.

Abstract

BACKGROUND: Atherosclerosis is a well-established inflammatory disease in which T helper 1 (Th1) cells play a key role. Regulatory T (Treg) cells drive a shift from Th1 to Th2 response and were shown to be reduced in atherosclerosis. ST2/interleukin (IL)-33 signal was found to promote Th2 response, attenuating atherosclerotic plaque progression. OBJECTIVES: To evaluate the effect of IL-33 on Treg cell number. METHODS: We employed flow cytometry to determine Treg cell number, as well as ST2 levels, among splenocytes of C57BL/61 vs ApoE-/- mice. Soluble ST2 (sST2) levels were detected by enzyme-linked immunosorbent assay. RESULTS: IL-33 contributed to an increase in Treg cells, but this association was attenuated in ApoE knockout (ApoE-/-) atherosclerotic mice. As a possible mechanism we demonstrated a reduction in the levels of CD4+ST2+ cells by flow cytometry, which is cotemporary to the previously described decrease in Treg cells in ApoE-/- mice. Additionally, the serum level of the soluble ST2 (sST2) decoy receptor was higher in ApoE-/- mice than in control animals. CONCLUSIONS: Our results suggest that a repressed ST2/ IL-33 signaling may contribute to the decrease in Treg cells observed in atherosclerosis.