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

- NKT cells regulate macrophage production of IL-1β via cytokine production.
- Among cytokines secreted by NKT cells, GM-CSF and IL-4 inversely influence IL-1β production.
- GM-CSF regulates LPS-mediated pro-IL-1β expression and inflammasome activation.
- IL-4 enhances M2-polarization of macrophages thereby inhibits IL-1β production.

Natural Killer T (NKT) cells are distinct T cell subset that link innate and adaptive immune responses. IL-1β, 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-1β 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-1β production by macrophages via regulating LPS-mediated pro-IL-1β expression and NLRP3-dependent inflammasome activation, whereas IL-4 enhanced M2-differentiation of macrophages and decreased IL-1β production. Together, our findings suggest the NKT cells have double-sided effects on IL-1β-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-1β in inflammatory diseases in vivo.

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