title: Adipose tissue macrophages induce PPARγ-high FOXP3(+) regulatory T cells.
abstract: Numerous regulatory T cells (Tregs) are present in adipose tissues compared with other lymphoid or non-lymphoid tissues. Adipose Tregs regulate inflammatory state and insulin sensitivity. However, the mechanism that maintains Tregs in adipose tissue remains unclear. Here, we revealed the contribution of adipose tissue macrophages (ATMs) to the induction and proliferation of adipose Tregs. ATMs isolated from mice under steady state conditions induced Tregs with high expression of PPARγ compared with splenic dendritic cells in vitro. Furthermore, ATMs from obese mice prompted the differentiation of PPARγ low Tregs. Adoptive transfer of ATMs induced differentiation and proliferation of Tregs, whereas depletion of ATMs by clodronate-liposome resulted in reduction of adipose Tregs, in vivo. Deficiency of anti-inflammatory adipocytokine, Adipoq, resulted in small proportions of ATMs and adipose Tregs without alteration of other immune cells in vivo. Therefore, these data suggest that the abundance of Tregs in adipose tissue could be partly attributed to the ability of ATMs to induce PPARγ-expressing Tregs.
authors.affiliation: Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2, Yamamdaoka, Suita, Osaka, Japan.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Onodera
authors.affiliation: Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2, Yamamdaoka, Suita, Osaka, Japan.
authors.forename: Atsunori
authors.initials: A
authors.lastname: Fukuhara
authors.affiliation: Academy of Immunology and Microbiology (AIM), Institute for Basic Science (IBS), Pohang 790-784, Korea.
authors.forename: Myoung Ho
authors.initials: MH
authors.lastname: Jang
authors.affiliation: Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2, Yamamdaoka, Suita, Osaka, Japan.
authors.forename: Jihoon
authors.initials: J
authors.lastname: Shin
authors.affiliation: Department of Immunology and Cell Biology, Osaka University Graduate School of Medicine &Frontier Biosciences, WPI-Immunology Frontier Research Center, 2-2, Yamamdaoka, Suita, Osaka, Japan.|JST, CREST, 5 Sanban-cho, Chiyoda-ku, Tokyo, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Aoi
authors.affiliation: Department of Immunology and Cell Biology, Osaka University Graduate School of Medicine &Frontier Biosciences, WPI-Immunology Frontier Research Center, 2-2, Yamamdaoka, Suita, Osaka, Japan.|JST, CREST, 5 Sanban-cho, Chiyoda-ku, Tokyo, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Kikuta
authors.affiliation: Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2, Yamamdaoka, Suita, Osaka, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Otsuki
authors.affiliation: Department of Immunology and Cell Biology, Osaka University Graduate School of Medicine &Frontier Biosciences, WPI-Immunology Frontier Research Center, 2-2, Yamamdaoka, Suita, Osaka, Japan.|JST, CREST, 5 Sanban-cho, Chiyoda-ku, Tokyo, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Ishii
authors.affiliation: Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2, Yamamdaoka, Suita, Osaka, Japan.
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
mesh_terms: D052242:Adiponectin / Q000172:deficiency / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004002:Clodronic Acid / Q000494:pharmacology; D059305:Diet, High-Fat; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000378:metabolism*; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism
chemical_list: D052242:Adiponectin; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D047495:PPAR gamma; D004002:Clodronic Acid