title: An MHC II-dependent activation loop between adipose tissue macrophages and CD4+ T cells controls obesity-induced inflammation.
abstract: An adaptive immune response triggered by obesity is characterized by the activation of adipose tissue CD4(+) T cells by unclear mechanisms. We have examined whether interactions between adipose tissue macrophages (ATMs) and CD4(+) T cells contribute to adipose tissue metainflammation. Intravital microscopy identifies dynamic antigen-dependent interactions between ATMs and T cells in visceral fat. Mice deficient in major histocompatibility complex class II (MHC II) showed protection from diet-induced obesity. Deletion of MHC II expression in macrophages led to an adipose tissue-specific decrease in the effector/memory CD4(+) T cells, attenuation of CD11c(+) ATM accumulation, and improvement in glucose intolerance by increasing adipose tissue insulin sensitivity. Ablation experiments demonstrated that the maintenance of proliferating conventional T cells is dependent on signals from CD11c(+) ATMs in obese mice. These studies demonstrate the importance of MHCII-restricted signals from ATMs that regulate adipose tissue T cell maturation and metainflammation.
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Soonchunhyang Institute of Medi-bio Science, Soonchunhyang University, Cheonan-si, Chungcheongnam-do 330-930, South Korea.
authors.forename: Kae Won
authors.initials: KW
authors.lastname: Cho
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Morris
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: DelProposto
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Lynn
authors.initials: L
authors.lastname: Geletka
authors.affiliation: Graduate Program in Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Zamarron
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Martinez-Santibanez
authors.affiliation: Department of Surgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Meyer
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Kanakadurga
authors.initials: K
authors.lastname: Singer
authors.affiliation: Department of Surgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Surgery, Ann Arbor Veteran's Administration Hospital, Ann Arbor, MI 48109, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: O'Rourke
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Graduate Program in Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA. Electronic address: clumeng@umich.edu.
authors.forename: Carey N
authors.initials: CN
authors.lastname: Lumeng
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000276:immunology*; D000818:Animals; D039521:CD11c Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D017353:Gene Deletion; D005802:Genes, MHC Class II; D006684:HLA-DR Antigens / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000276:immunology*
chemical_list: D039521:CD11c Antigen; D006684:HLA-DR Antigens