title: M2-specific reduction of CD1d switches NKT cell-mediated immune responses and triggers metaflammation in adipose tissue.
abstract: Metaflammation is responsible for several metabolic syndromes, such as type 2 diabetes. However, the mechanisms by which metabolic disorders trigger metaflammation remain unclear. We identified a cell type-specific downregulation of CD1d expression in M2 macrophages during the progression of obesity prior to the onset of inflammation in visceral adipose tissues. A reduction in CD1d expression influenced the ability of M2 macrophages to present antigens and caused a change in antigen-presenting cells from M2 macrophages to M1 macrophages. With CD1d conditional knockout (KO) mice, we further demonstrated that natural killer T (NKT) cell activation by M2 macrophages inhibited metaflammation and insulin resistance by promoting Th2 responses and M2 polarization in visceral adipose tissues of obese mice, whereas NKT cell activation by M1 macrophages exacerbated metaflammation and insulin resistance by promoting Th1 responses and inhibiting M2 polarization. Our results suggest that an M2-specific reduction of CD1d is an initiating event that switches NKT cell-mediated immune responses and disrupts the immune balance in visceral adipose tissues in obese mice.
authors.affiliation: CAS Key Laboratory of Innate Immunity and Chronic Disease, CAS Center for Excellence in Molecular Cell Science, School of Life Sciences and Medical Center, University of Science and Technology of China, 230027, Hefei, China.|Innovation Center for Cell Signaling Network, Hefei National Laboratory for Physical Sciences at Microscale, 230027, Hefei, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory of Innate Immunity and Chronic Disease, CAS Center for Excellence in Molecular Cell Science, School of Life Sciences and Medical Center, University of Science and Technology of China, 230027, Hefei, China.|Innovation Center for Cell Signaling Network, Hefei National Laboratory for Physical Sciences at Microscale, 230027, Hefei, China.
authors.forename: Rufeng
authors.initials: R
authors.lastname: Xue
authors.affiliation: CAS Key Laboratory of Innate Immunity and Chronic Disease, CAS Center for Excellence in Molecular Cell Science, School of Life Sciences and Medical Center, University of Science and Technology of China, 230027, Hefei, China.|Innovation Center for Cell Signaling Network, Hefei National Laboratory for Physical Sciences at Microscale, 230027, Hefei, China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Zhu
authors.affiliation: CAS Key Laboratory of Innate Immunity and Chronic Disease, CAS Center for Excellence in Molecular Cell Science, School of Life Sciences and Medical Center, University of Science and Technology of China, 230027, Hefei, China.|Innovation Center for Cell Signaling Network, Hefei National Laboratory for Physical Sciences at Microscale, 230027, Hefei, China.
authors.forename: Sicheng
authors.initials: S
authors.lastname: Fu
authors.affiliation: CAS Key Laboratory of Innate Immunity and Chronic Disease, CAS Center for Excellence in Molecular Cell Science, School of Life Sciences and Medical Center, University of Science and Technology of China, 230027, Hefei, China.|Innovation Center for Cell Signaling Network, Hefei National Laboratory for Physical Sciences at Microscale, 230027, Hefei, China.
authors.forename: Zuolong
authors.initials: Z
authors.lastname: Chen
authors.affiliation: CAS Key Laboratory of Innate Immunity and Chronic Disease, CAS Center for Excellence in Molecular Cell Science, School of Life Sciences and Medical Center, University of Science and Technology of China, 230027, Hefei, China.|Innovation Center for Cell Signaling Network, Hefei National Laboratory for Physical Sciences at Microscale, 230027, Hefei, China.
authors.forename: Rongbin
authors.initials: R
authors.lastname: Zhou
authors.affiliation: CAS Key Laboratory of Innate Immunity and Chronic Disease, CAS Center for Excellence in Molecular Cell Science, School of Life Sciences and Medical Center, University of Science and Technology of China, 230027, Hefei, China.|Innovation Center for Cell Signaling Network, Hefei National Laboratory for Physical Sciences at Microscale, 230027, Hefei, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Tian
authors.affiliation: CAS Key Laboratory of Innate Immunity and Chronic Disease, CAS Center for Excellence in Molecular Cell Science, School of Life Sciences and Medical Center, University of Science and Technology of China, 230027, Hefei, China. baili@ustc.edu.cn.|Innovation Center for Cell Signaling Network, Hefei National Laboratory for Physical Sciences at Microscale, 230027, Hefei, China. baili@ustc.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Bai
mesh_terms: D000273:Adipose Tissue / Q000473:pathology*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D055610:Antigens, CD1d / Q000378:metabolism*; D018450:Disease Progression; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D007109:Immunity; D007249:Inflammation / Q000276:immunology* / Q000473:pathology*; D007333:Insulin Resistance; D008264:Macrophages / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology*; D009765:Obesity / Q000473:pathology
chemical_list: D055610:Antigens, CD1d; D005947:Glucose
keywords: CD1d; NKT cells; macrophage; metaflammation