GM-CSF and IL-4 produced by NKT cells inversely regulate IL-1β production by macrophages (INC6P.402)

Abstract

NKT cell is a distinct T cell subset that links innate and adaptive immune responses. IL-1β, produced by various immune cells, plays critical role in the regulation of innate immunity in vivo. However, it is unclear whether NKT cells regulate IL-1β production in vivo. Here, we demonstrate that NKT cells regulate production of IL-1β by macrophages via producing GM-CSF and IL-4. Among cytokines secreted from NKT cells, GM-CSF enhanced IL-1β production by macrophages through regulating pro-IL-1β expression and NLRP3-dependent inflammasome activation, whereas IL-4 enhanced M2-differentiation of macrophages, thereby decreasing IL-1β production. Furthermore, NKT cells aggravated IL-1β-mediated peritonitis by producing GM-CSF, but attenuated peritonitis via producing IL-4. Taken together, our findings suggest the NKT cells exert double-sided effects on IL-1β-mediated innate immune responses by producing IL-4 and IL-1β.