Ahn Sehee, Jeong Dongjin, Oh Sae Jin, Ahn Jiye, Lee Seung Hyo, Chung Doo Hyun
Laboratory of Immune Regulation in Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
Graduate School of Medical Science and Engineering, Biomedical Research Center, Korean Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea.
Immunol Lett. 2017 Feb;182:50-56. doi: 10.1016/j.imlet.2017.01.003. Epub 2017 Jan 4.
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.
自然杀伤T（NKT）细胞是连接固有免疫和适应性免疫反应的独特T细胞亚群。由各种免疫细胞产生的白细胞介素-1β（IL-1β）在体内固有免疫调节中起关键作用。然而，尚不清楚NKT细胞是否调节巨噬细胞产生IL-1β。为了解决这个问题，我们在TCR刺激和炎性小体激活剂存在的情况下共培养了NKT细胞和腹膜巨噬细胞。在NKT细胞分泌的细胞因子中，粒细胞-巨噬细胞集落刺激因子（GM-CSF）通过调节脂多糖（LPS）介导的前体IL-1β表达和NLRP3依赖性炎性小体激活来增强巨噬细胞产生IL-1β，而IL-4则增强巨噬细胞的M2分化并减少IL-1β的产生。总之，我们的研究结果表明NKT细胞通过产生IL-4和GM-CSF对IL-1β介导的固有免疫反应具有双面影响。这些发现可能有助于全面了解NKT细胞在体内炎症性疾病中介导IL-1β促炎作用的调节机制。
