title: Th17 cytokines differentiate obesity from obesity-associated type 2 diabetes and promote TNFα production.
abstract: OBJECTIVE
  T cell inflammation plays pivotal roles in obesity-associated type 2 diabetes (T2DM). The identification of dominant sources of T cell inflammation in humans remains a significant gap in understanding disease pathogenesis. It was hypothesized that cytokine profiles from circulating T cells identify T cell subsets and T cell cytokines that define T2DM-associated inflammation.
  
  
  METHODS
  Multiplex analyses were used to quantify T cell-associated cytokines in αCD3/αCD28-stimulated PBMCs, or B cell-depleted PBMCs, from subjects with T2DM or BMI-matched controls. Cytokine measurements were subjected to multivariate (principal component and partial least squares) analyses. Flow cytometry detected intracellular TNFα in multiple immune cell subsets in the presence/absence of antibodies that neutralize T cell cytokines.
  
  
  RESULTS
  T cell cytokines were generally higher in T2DM samples, but Th17 cytokines are specifically important for classifying individuals correctly as T2DM. Multivariate analyses indicated that B cells support Th17 inflammation in T2DM but not control samples, while monocytes supported Th17 inflammation regardless of T2DM status. Partial least squares regression analysis indicated that both Th17 and Th1 cytokines impact %HbA1c.
  
  
  CONCLUSIONS
  Among various T cell subsets, Th17 cells are major contributors to inflammation and hyperglycemia and are uniquely supported by B cells in obesity-associated T2DM.
authors.affiliation: Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Blanche
authors.initials: B
authors.lastname: Ip
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Cilfone
authors.affiliation: Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Anna C
authors.initials: AC
authors.lastname: Belkina
authors.affiliation: Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: DeFuria
authors.affiliation: Department of Pathology, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Madhumita
authors.initials: M
authors.lastname: Jagannathan-Bogdan
authors.affiliation: Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Ramya
authors.initials: R
authors.lastname: Kuchibhatla
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Marie E
authors.initials: ME
authors.lastname: McDonnell
authors.affiliation: Biosciences Division, EMD-Millipore, St. Charles, Missouri, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xiao
authors.affiliation: Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Kepler
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Apovian
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Lauffenburger
authors.affiliation: Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, USA.|Department of Pathology, Boston University School of Medicine, Boston, Massachusetts, USA.|Department of Molecular and Cell Biology, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Nikolajczyk
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000276:immunology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D009765:Obesity / Q000150:complications* / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D055815:Young Adult
chemical_list: D016207:Cytokines; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha