GM-CSF and IL-4 produced by NKT cells inversely regulate IL-1β production by macrophages

Natural Killer T(NKT) cells are distinct T cell subset that link innate and adaptive immune responses. IL-1 beta , produced by various immune cells, plays a key role in the regulation of innate immunity in vivo. However, it is unclear whether NKT cells regulate IL-1 beta production by macrophages. To address this, we co-cultured NKT cells and peritoneal macrophages in the presence of TCR stimulation and inflammasome activators. Among cytokines secreted from NKT cells, GM-CSF enhanced IL-1 beta production by macrophages via regulating LPS-mediated pro-IL-1 beta expression and NLRP3-dependent inflammasome activation, whereas IL-4 enhanced M2-differentiation of macrophages and decreased IL-1 beta production. Together, our findings suggest the NKT cells have double-sided effects on IL-1 beta-mediated innate immune responses by producing IL-4 and GM-CSF. These findings may be helpful for a comprehensive understanding of NKT cell-mediated regulatory mechanisms of the pro-inflammatory effects of IL-1 beta in inflammatory diseases in vivo. (C)2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.