title: GM-CSF and IL-4 produced by NKT cells inversely regulate IL-1β production by macrophages.
abstract: 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.
authors.affiliation: Laboratory of Immune Regulation in Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sehee
authors.initials: S
authors.lastname: Ahn
authors.affiliation: Laboratory of Immune Regulation in Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Dongjin
authors.initials: D
authors.lastname: Jeong
authors.affiliation: Laboratory of Immune Regulation in Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sae Jin
authors.initials: SJ
authors.lastname: Oh
authors.affiliation: Laboratory of Immune Regulation in Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jiye
authors.initials: J
authors.lastname: Ahn
authors.affiliation: Graduate School of Medical Science and Engineering, Biomedical Research Center, Korean Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea.
authors.forename: Seung Hyo
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea; Laboratory of Immune Regulation in Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea; Ischemic/Hypoxia Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: doohyun@snu.ac.kr.
authors.forename: Doo Hyun
authors.initials: DH
authors.lastname: Chung
mesh_terms: D000818:Animals; D020170:Caspase 1 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D058847:Inflammasomes / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism*
chemical_list: D016207:Cytokines; D058847:Inflammasomes; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D020170:Caspase 1
keywords: GM-CSF; IL-1b; IL-4; Macrophages; NKT cells